2013年1月～2013年12月

᳃ ᳍ ᳍ ᳈ Წ ᲫᲲ Ჰ ᲧᲯᲯ Ც Ჱ
ʮᣃငಅ‫ܖٻ‬ዮӳဃԡᅹ‫ܖ‬ᢿ ࠰‫إ‬
#PPWCN4GRQTVQHVJG(CEWNV[QH.KHG5EKGPEGU
-[QVQ5CPI[Q7PKXGTUKV[
ģᇹᲮӭĤ
ᲬᲪᲫᲭ
࠯঺ ࠰
⬻⾲㠃࠿ࡽග࡛┤᥋⬻⾑ὶኚ໬ࢆィ ࡍࡿ᪂ᢏ⾡
ࡇࢀࡲ࡛ࠊ㢌ࡢ⾲㠃࡟」ᩘࡢග※࡜ཷගࢭࣥࢧ࣮ࢆ㓄⨨ࡋࠊࢭࣥࢧ࣮ࡢ᝟ሗࢆࡶ࡜
࡟⬻⾑ὶࡢኚ໬ࢆ⬻⾲㠃ୖࡢศᕸ࡜ࡋ࡚ ḟඖ⏬ീ࡜ࡋ࡚⾲♧ࡍࡿࠕගࢺ࣏ࢢࣛࣇ࢕
࣮ࠖ࡜࠸࠺ᢏ⾡ࡣᐇ⏝໬ࡉࢀ࡚࠸ࡲࡋࡓࡀࠊ✵㛫ゎീᗘࡀ FP ⛬ᗘ࡛㸦FP ᱁Ꮚ≧ࣉ
࣮ࣟࣈ㓄⨨ࡢሙྜ㸧ࠊ⬻௨እࡢ⓶⭵⤌⧊࡞࡝࠿ࡽಙྕࡀΰධࡍࡿྍ⬟ᛶࡀ࠶ࡾࡲࡋࡓࠋ
௒ᅇࠊୡ⏺࡟ඛ㥑ࡅࠊ㯞㓉ࡋࡓ࣑ࢽࣈࢱࢆ⏝࠸࡚኱⬻⓶㉁⾲㠃࠿ࡽࢲ࢖ࣞࢡࢺ࡟ග
࡛⬻ࡢ⾑ὶ཯ᛂࢆィ ࡋࠊ⬻άືࢆ㧗⢭ᗘࡢ㸰ḟඖ࣐ࢵࣉ࡜ࡋ࡚⾲⌧ࡍࡿᡭἲࡢ㛤Ⓨ
࡟ᡂຌࡋࡲࡋࡓࠋࡇࡢࠕࢲ࢖ࣞࢡࢺගࢺ࣏ࢢࣛࣇ࢕࣮ἲࠖ࡟ࡼࡾࠊ⬻ࡢ⾲㠃࡟」ᩘࡢ
ග※࡜ཷගࢭࣥࢧ࣮ࢆ PP 㛫㝸࡛㓄⨨ࡋࠊ⣙ PP ࡢ㧗⢭ᗘ࡛ࠊ␗࡞ࡿ఩⨨ࡢ⬻άືࢆ
ศ㞳ࡍࡿࡇ࡜ࡀྍ⬟࡟࡞ࡾࡲࡋࡓࠋ
௒ᚋࠊ࣑ࢽࣈࢱ࡟ࡼࡿᇶ♏ᐇ㦂ࢆ㐍ࡵࠊࣄࢺࡢ⬻⚄⤒እ⛉ᡭ⾡୰ࡢ⬻ᶵ⬟ࣔࢽࢱࣜ
ࣥࢢ࡬ࡢ⮫ᗋᛂ⏝ᐇ⌧ࢆ┠ᣦࡋ࡚࠸ࡁࡲࡍࠋ
࡞࠾ࠊࡇࡢᡂᯝࡣ⮬἞་⛉኱Ꮫࠊ୰ኸ኱Ꮫࠊி㒔⏘ᴗ኱Ꮫࡽࡢࢢ࣮ࣝࣉ࡟ࡼࡿඹྠ
◊✲࡛ᚓࡽࢀࡓࡶࡢ࡛ࡍࠋ
8JD0HWDOKWWSG[GRLRUJMQHXURLPDJH
┠ ḟ
ᕳ㢌ゝ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ◊✲ᐊ࣓ࣥࣂ࣮࣭஦ົᐊࢫࢱࢵࣇ୍ぴ࣭඲Ꮫጤဨ఍ጤဨ୍ぴ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ 㸰㸮㸯㸱ᖺάືグ㘓 ⏕࿨ࢩࢫࢸ࣒Ꮫ⛉ ⏕࿨ࢩࢫࢸ࣒Ꮫ⛉ࡢᩍ⫱◊✲άື ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᯈ 㔝 ┤ ᶞ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ఀ ⸨ ⥔ ᫛ ᐈဨᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ 㯮 ᆏ ග ᩍ ᤵ㸦Ꮫ㒊㛗㸧 ࣭࣭࣭࣭࣭࣭࣭࣭࣭ బ ⸨ ㈼ ୍ ᩍ ᤵ㸦Ꮫ⛉୺௵㸧 ࣭࣭࣭࣭࣭࣭࣭࣭ ᔱ ᮏ ఙ 㞝 ᐈဨᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ℩ ᑿ ⨾ 㕥 ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ୰ ⏣ ༤ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ Ọ ⏣ ࿴ ᏹ ᐈဨᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ୰ ᮧ ᬸ ᏹ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ὾ ༓ ᑜ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ⚟ ஭ ᡂ ⾜ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ඵ ᮡ ㈆ 㞝 ᐈဨᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᶓ ᒣ ㅬ ᩍ ᤵ㸦๪Ꮫ⛉୺௵㸧 ࣭࣭࣭࣭࣭࣭࣭ ྜྷ ⏣ ㈼ ྑ ᐈဨᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ⏕࿨㈨※⎔ቃᏛ⛉ ⏕࿨㈨※⎔ቃᏛ⛉ࡢᩍ⫱◊✲άື ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ 㔠 Ꮚ ㈗ ୍ ෸ᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ Ἑ 㑔 ᫛ ෸ᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᮌ ᮧ ᡂ ௓ ෸ᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ 㧗 ᶫ ⣧ ୍ ෸ᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ὠ ୗ ⱥ ᫂ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᑎ ᆅ ᚭ ᩍ ᤵ㸦Ꮫ⛉୺௵㸧 ࣭࣭࣭࣭࣭࣭࣭࣭ 㔝 ᮧ ဴ 㑻 ᩍ ᤵ㸦๪Ꮫ⛉୺௵㸧 ࣭࣭࣭࣭࣭࣭࣭ ᮏ ᶫ ೺ ෸ᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᒣ ᓊ ༤ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ື≀⏕࿨་⛉Ꮫ⛉ ື≀⏕࿨་⛉Ꮫ⛉ࡢᩍ⫱◊✲άື ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ኱ ᵳ බ ୍ ᐈဨᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ຍ ⸨ ၨ Ꮚ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ௒ 㔝 වḟ㑻 ຓ ᩍ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ 㰻 ⸨ ᩄ அ ᩍ ᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᰁ ㇂ ᱻ ຓ ᩍ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ 㧘 ᱓ ᘯ ᶞ ෸ᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ➉ ෆ ᐇ ᩍ ᤵ㸦Ꮫ⛉୺௵㸧 ࣭࣭࣭࣭࣭࣭࣭࣭ Ჴ ᶫ 㟹 ⾜ ຓ ᩍ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ す 㔝 ె ௨ ෸ᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ๓ ⏣ ⛅ ᙪ ᩍ ᤵ㸦๪Ꮫ⛉୺௵㸧 ࣭࣭࣭࣭࣭࣭࣭ ᯇ ᮏ ⪔ ୕ ᐈဨᩍᤵ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᮧ ⏣ ⱥ 㞝 ᩍ ᤵ㸦๪Ꮫ㒊㛗㸧 ࣭࣭࣭࣭࣭࣭࣭࣭ 㸰㸮㸯㸱ᖺ ⥲ྜ⏕࿨⛉Ꮫ㒊 ◊✲ࢺࣆࢵࢡࢫ ࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭࣭ ᕳ㻌 㢌㻌 ゝ㻌
⥲ྜ⏕࿨⛉Ꮫ㒊㛗㻌
㯮㻌 ᆏ㻌 㻌 㻌 ග㻌
㻌 ⥲ྜ⏕࿨⛉Ꮫ㒊ࡣࠊᖹᡂ㸰㸰ᖺ࡟㛤タࡉࢀࡓᮏᏛ࡛ࡣ᭱ࡶ᪂ࡋ࠸Ꮫ㒊࡛ࡍࠋึ௦Ꮫ㒊㛗ࡢỌ⏣࿴ᏹᩍ
ᤵࡢᏛ㒊㛗㏥௵ࢆཷࡅࠊ᫖ᖺ㸲᭶࡟⚾ࡀḟᮇᏛ㒊㛗ࢆᣏ࿨ࡋࡲࡋࡓࠋὸᏛ㠀ᡯࡢ⚾࡟ࡣࠊᑓ௵ᩍဨ㸱
㸳ྡࠊࣉࣟࢪ࢙ࢡࢺຓᩍ㸯㸰ྡ࡟ຍ࠼ࠊ࣏ࢫࢻࢡࠊᐈဨ◊✲ဨ࡞࡝ࡢከࡃࡢᵓᡂဨࢆᢪ࠼ࡿ⥲ྜ⏕࿨
⛉Ꮫ㒊ࡢ⯦ྲྀࡾࡣⲴࡀ㔜ࡃࠊᏛ㒊㐠Ⴀ࡟୙Ᏻࢆឤࡌࡲࡋࡓࡀࠊఱ࡜࠿ࡇࡢ⃭ືࡢ㸯ᖺࢆ஌ࡾษࡿࡇ࡜
ࡀ࡛ࡁࡲࡋࡓࠋࡇࢀࡶࡦ࡜࠼࡟ⓙᵝࡢࡈ༠ຊ࡜ࡈ⌮ゎ࡟ࡼࡿࡶࡢ࡜ឤㅰࡢẼᣢࡕ୍࡛ᮼ࡛ࡍࠋ
ᖹᡂ㸰㸳ᖺᗘࢆࡶࡗ࡚㸲ᖺ㛫ࡢᏛ㒊᏶ᡂᖺᗘࢆ⤊࠼ࡿ⥲ྜ⏕࿨⛉Ꮫ㒊࡛ࡣࠊ㸯ᖺࢆ࠿ࡅ࡚ᩍ⫱࣭◊
✲඲యࢆ᳨ドࡋࡲࡋࡓࠋᩍ⫱㠃࡛ࡣ࣒࢝ࣜ࢟ࣗࣛࢆᨵゞࡋࠊࡼࡾຠ⋡ⓗ࡞ࡶࡢࢆసᡂࡋࡲࡋࡓࠋࡲࡓ
ᮏᖺᗘ࠿ࡽࠊᩥ㒊⛉Ꮫ┬᥇ᢥࡢ⌮⣔ࢢ࣮ࣟࣂࣝேᮦ⫱ᡂ஦ᴗࡀᮏ᱁ⓗ࡟ጞࡲࡾࠊ඘ᐇࡋࡓⱥㄒᩍ⫱ࡀ
ᐇ᪋ࡉࢀࡲࡍࠋ◊✲㠃࡛ࡣࠊᮏᏛ㒊⊂⮬ࡢ◊✲ᨭ᥼ไᗘ࡛࠶ࡿࣉࣟࢪ࢙ࢡࢺ◊✲ᨭ᥼ไᗘ࡟ࡘ࠸࡚㆟
ㄽࢆ㔜ࡡ࡚ࡁࡲࡋࡓࠋࡲࡓࠊ⥲ྜ⏕࿨⛉Ꮫ㒊ࢆᇶ♏Ꮫ㒊࡜ࡋ࡚ࠊ኱Ꮫ㝔⏕࿨⛉Ꮫ◊✲⛉㸦ಟኈㄢ⛬㸧
ࢆ⏦ㄳࡋ࡚࠾ࡾࡲࡋࡓࡀࠊᩥ㒊⛉Ꮫ┬ࡼࡾㄆྍࢆཷࡅࠊᬕࢀ࡚ࡇࡢ㸲᭶࠿ࡽ᪂◊✲⛉ࢆ㛤タࡍࡿࡇ࡜
ࡀ࡛ࡁࡲࡋࡓࠋࡇࢀࢆࡶࡗ࡚ࠊᏛ㒊࠿ࡽ኱Ꮫ㝔ࡲ୍࡛㈏ࡋ࡚ᩍ⫱࣭◊✲࡟ྲྀࡾ⤌ࡴ⎔ቃࡀᩚഛࡉࢀࡲ
ࡋࡓࠋ
ࡇࡢ㸱᭶࡟ึࡵ࡚ࡢ༞ᴗ⏕ࢆ㏦ࡾฟࡋࡓࡇ࡜ࡣࠊᮏᏛ㒊࡟࡜ࡗ࡚኱ኚᎰࡋ࠸ࡇ࡜࡛ࡋࡓࠋᖾ࠸࡟ࡶ
ᑵ⫋ࡣ㡰ㄪ࡛ࠊᑵ⫋ෆᐃ⋡ࡣ㠀ᖖ࡟㧗࠸ࡶࡢ࡛ࡋࡓࠋࡲࡓࠊ኱Ꮫ㝔࡟ࡶከࡃࡢᏛ⏕ࡀ㐍Ꮫࡋࠊ᪂◊✲
⛉࡟ࡶᐃဨࢆୖᅇࡿෆ㒊㐍Ꮫ⪅ࡀ࠶ࡾࡲࡋࡓࠋ༞ᴗ⏕ࡢⓙࡉࢇࡣࠊࡑࢀࡒࢀ㐍㊰ࡣ␗࡞ࡾࡲࡍࡀࠊ኱
Ꮫ࡛ᇵࡗ࡚ࡁࡓࡇ࡜ࢆ༑ศⓎ᥹ࡋ࡚ࡈά㌍ࡉࢀࡿࡇ࡜ࢆ㢪ࡗ࡚࠸ࡲࡍࠋⓙࡉࢇࡢ㊊㊧ࡀᚋ㍮㐩ࡢṌࡴ
࡭ࡁ㐨࡜࡞ࡗ࡚࠸ࡁࡲࡍࠋ
ࡲࡓࠊᖹᡂ㸰㸳ᖺᗘࢆࡶࡗ࡚㸳ྡࡢᩍဨ㸦⏕࿨ࢩࢫࢸ࣒Ꮫ⛉࠿ࡽࡣఀ⸨ࠊ⚟஭ࠊඵᮡࠊྜྷ⏣ྛᩍᤵࠊ
ື≀⏕࿨་⛉Ꮫ⛉࠿ࡽࡣ኱ᵳᩍᤵ㸧ࡀ㏥⫋ࡉࢀࡲࡋࡓࠋඛ⏕᪉࡟ࡣࠊᏛ㒊ࡢタ❧࠿ࡽ௒᪥࡟⮳ࡿࡲ࡛
Ꮫ㒊ࢆ≌ᘬࡋ࡚࠸ࡓࡔࡁࡲࡋࡓࠋᮏᏛ㒊ࡀண᝿ࢆୖᅇࡿ㡰ㄪ࡞ࢫࢱ࣮ࢺࢆษࡿࡇ࡜ࡀ࡛ࡁࡓࡢࡶࠊඛ
⏕᪉ࡢࡈᑾຊࡢࡓࡲࡶࡢ࡜ឤㅰ⮴ࡋࡲࡍࠋ୍᪉ࠊ᪂つᩍဨ᥇⏝ே஦ࡶేࡏ࡚⾜࠸ࠊ㸲᭶࡟ࡣ᪂ࡋࡃ㸲
ྡࡢᩍဨࢆ࠾㏄࠼ࡋࡲࡋࡓࠋࡇࢀ࠿ࡽࡣ᪂ࡋ࠸ඛ⏕᪉࡜ຊࢆྜࢃࡏ࡚ࠊࡼࡾ⣲ᬕࡽࡋ࠸Ꮫ㒊࡟ࡋ࡚࠸
࠿ࡡࡤ࡞ࡾࡲࡏࢇࠋ
ࡇࡢࡼ࠺࡟ࠊᏛ㒊᏶ᡂᖺᗘࢆ⤊࠼ࡓ⥲ྜ⏕࿨⛉Ꮫ㒊ࡣࠊḟࡢࢫࢸ࣮ࢪ࡟ྥ࠿ࡗ࡚ࢫࢱ࣮ࢺࢆษࡾࡲ
ࡋࡓࠋࡉࡽ࡟௒ᖺᗘ࡟ࡣࠊ⏕࿨⛉Ꮫ◊✲⛉༤ኈᚋᮇㄢ⛬ࡢタ⨨⏦ㄳࡢ‽ഛࢆࡣࡌࡵࡲࡍࠋ༤ኈᚋᮇㄢ
⛬ࢆ㛤タࡋ࡚㧗࠸ࣞ࣋ࣝࡢᩍ⫱࣭◊✲άືࢆ⾜࠸ࠊ᭱ึࡢᏛ఩ྲྀᚓ⪅ࢆ㏦ࡾฟࡋ࡚ࡣࡌࡵ୍࡚ே๓ࡢ
Ꮫ㒊࣭◊✲⛉࡜࠸࠼ࡿࡢ࡛ࡋࡻ࠺ࠋࡑࢀࡲ࡛ࡓࡺࡲࡠ๓㐍ࡀᚲせ࡛ࡍࠋ
Ꮫ㒊࡜ࡋ࡚⬚✺ࡁඵ୎ࡢ኱ኚ࡞᫬ᮇࢆྥ࠿࠼࡚࠾ࡾࡲࡍࡀࠊᩍ⫱࣭◊✲ࡢᡭࢆỴࡋ࡚⦆ࡵࡿࢃࡅ࡟
ࡣ⾜ࡁࡲࡏࢇࠋᮏᏛ㒊ࡣ⮬ࡽࡢάືࢆ᳨ドࡍࡿࡓࡵ࡟ࠊᏛ㒊⊂⮬ࡢྲྀࡾ⤌ࡳ࡜ࡋ࡚ᖺሗࢆⓎ⾜ࡋ࡚࠸
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±
±
細胞外マトリックス
成長因子など
（瀬尾：癌細胞と神経細胞におけるシグナル伝達）
（板野：癌微小環境形成の分子機構と癌幹細胞制御）
（八杉：器官形成におけるシグナル伝達と細胞間相互作用）
P
細胞膜
（佐藤：卵細胞と癌細胞におけるシグナル伝達）
子
体／
P
分
接着
受容
各種
ゴルジ体
シグナル伝達
（中村：ゴルジ体の形成と機能）
（横山：空胞系プロトンポンプの分子機構）
核
小胞体
（嶋本：翻訳過程における分子機械のナノバイオロジー）
（伊藤：リボソーム上での合成途上ペプチドのはたらき）
ムチン
（永田：タンパク質の品質管理機構とオルガネラ恒常性）
（中田：腫瘍細胞の悪性化と免疫能の低下）
糖鎖
（黒坂、福井：
神経細胞の糖鎖の合成と機能）
ミトコンドリア
（吉田：エネルギー産生、タンパク質の折れたたみ）
神経シナプス
±
（浜：シナプス形成と細胞外マトリックス）
±
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±
科目名
配当学年
担当教員
フレッシャーズセミナー
1
伊藤、吉田、黒坂、福井、永田、瀬尾、佐藤、八杉、中田、
嶋本、中村、浜、板野、横山
生物学通論Ａ、Ｂ
1
八杉、嶋本
化学通論Ａ、Ｂ
1
横山
生命システム概論
1
吉田、永田
物質生物化学
1
黒坂、浜
分子生物学
2
伊藤、瀬尾
遺伝子工学
2
伊藤、嶋本
代謝生物化学
2
吉田、中田
細胞生物学
2
福井、永田
発生生物学
2
佐藤、八杉
システム生物学
3
中村、板野
バイオ解析科学
3
中村、板野
タンパク質制御システム
3
吉田、永田
糖鎖生物学
3
福井、中田
細胞情報システム学
3
瀬尾
免疫学
3
中田
神経生物学
3
浜
構造生物学
3
横山
腫瘍生物学
3
佐藤
再生システム学
3
八杉
放射線生物学
3
黒坂
3
板野
薬理学
生命システム演習Ⅰ、Ⅱ、Ⅲ
1, 2
瀬尾、板野、横山、黒坂、中村
生命システム英語購読Ⅰ、Ⅱ、Ⅲ
2, 3
黒坂、嶋本、吉田、中田、伊藤、永田
生物学実験
生命システム実習Ⅰ、Ⅱ
1
2, 3
基礎特別研究
3
応用特別研究
4
福井、佐藤、中村、浜
伊藤、吉田、黒坂、福井、永田、瀬尾、佐藤、八杉、中田、
嶋本、中村、浜、板野、横山
伊藤、吉田、黒坂、福井、永田、瀬尾、佐藤、八杉、中田、
嶋本、中村、浜、板野、横山
伊藤、吉田、黒坂、福井、永田、瀬尾、佐藤、八杉、中田、
嶋本、中村、浜、板野、横山
（注：化学実験は非常勤講師によって行われている。）
ᩍᤵ㻌 ᯈ㔝㻌 ┤ᶞ
ᢠ⪁໬་Ꮫ◊✲ᐊ
Prof. Naoki Itano, Ph.D.㻌
㻸㼍㼎㼛㼞㼍㼠㼛㼞㼥㻌㼛㼒㻌㻭㼚㼠㼕㻙㻭㼓㼕㼚㼓㻌㻹㼑㼐㼕㼏㼕㼚㼑㻌
㻌
䠍䠊◊✲ᴫせ㻌
䛾せᅉ䛸⪃䛘䜙䜜䚸᰿἞ⓗ἞⒪䛾ᶆⓗ䛸䛧䛶㔜せど䛥䜜
㻌 㧗㱋໬♫఍䛾ᛴ㏿䛺㐍⾜䜢⫼ᬒ䛸䛧䛶䚸௓ㆤ䛺䛹ᵝ䚻
䛶䛔䜛䚹㻌
䛺ၥ㢟䛾ゎỴ 䛜ᛴົ䛾ㄢ 㢟䛸䛺䛳䛶䛔䜛䚹ᙜ◊✲ᐊ 䛾
⒴ᖿ⣽⬊䛿ṇᖖᖿ⣽⬊䛸ྠᵝ䛻䚸≉Ṧ䛺ᚤᑠ⎔ቃ㻔ᖿ
┠ᶆ䛿䚸⪁໬䛻≉ᚩⓗ䛺⑓ⓗ䛺≧ែ䛻௓ධ䛧䚸㛗ᑑ䛾
⣽⬊䝙䝑䝏㻕ෆ䛷⏕Ꮡ䛧䚸䛭䛾ᖿ⣽⬊ᛶ䜢⥔ᣢ䛧䛶䛔䜛䛸
㉁䠄ඖẼ䛻㛗ᑑ䜢ாཷ䛷䛝䜛≧ែ䠅䜢☜ಖ䛩䜛䛯䜑䛾㠉
⪃䛘䜙䜜䛶䛔䜛䚹ᚑ䛳䛶䚸⒴ᖿ⣽⬊䛾ᖿ⣽⬊ᛶ䜢႙ኻ䛥
᪂ⓗ䛺ᢏ⾡䜢☜❧䛩䜛䛣䛸䛷䛒䜛䚹ᢠ⪁໬་Ꮫ◊✲ᐊ䛷
䛫䚸ᝏᛶᙧ㉁㌿᥮䜢㜼Ṇ䛩䜛䛯䜑䛻䛿䚸⒴ᖿ⣽⬊䝙䝑䝏
䛿䚸䛣䛾┠ⓗ䛾䛯䜑䚸ศᏊ⏕≀Ꮫ䚸⣽⬊⏕≀Ꮫ䚸⏕໬Ꮫ䚸
䜢ᶆⓗ䛸䛩䜛䛣䛸䛜㔜せ䛷䛒䜛䚹ᮏ◊✲䛾୺┠ⓗ䛿䚸⒴
䛭䛧䛶䚸㑇ఏᏊᕤ Ꮫ䛾ඛ➃ ᢏ⾡䜢㥑౑䛧䛶䚸௨ୗ䛾◊
ᖿ⣽⬊䝙䝑䝏䛾ᙧᡂ䜢ᨭ㓄䛧䛶䛔䜛⣽⬊ᡂศཬ䜃ศᏊ
✲ㄢ㢟䛻ྲྀ䜚⤌䜣䛷䛔䜛䚹㻌
䜢ྠᐃ䛧䚸䛭䛾ᙧᡂ䜢䝁䞁䝖䝻䞊䝹䛩䜛䛣䛸䛻䜘䜚䚸⒴䜢ఇ
㻌
╀䛻ᑟ䛟䛯䜑䛾᪂つ἞⒪ἲ䜢☜❧䛩䜛䛣䛸䛷䛒䜛䚹㻌
䠍䠉䠍㻦䝠䜰䝹䝻䞁㓟⏕ྜᡂᶵᵓ䛾ゎ᫂䛸䜰䞁䝏䜶䜲䝆䞁䜾
ᢏ⾡䜈䛾ᒎ㛤㻌
㛵⠇ᶵ⬟䛾పୗ䛜ཎᅉ䛷ᐷ䛯䛝䜚䛻䛺䜛㧗㱋⪅䛜ቑ
䛘䛶䛔䜛䚹䛣䛾せᅉ䛸䛧䛶䚸㛵⠇䛷䜽䝑䝅䝵䞁䜔₶⁥䛾ᙺ
๭䜢䛩䜛䝠䜰䝹䝻䞁㓟䛾ῶᑡ䛜䛒䜛䚹䝠䜰䝹䝻䞁㓟䛿䚸㻺㻙
䜰䝉䝏䝹䜾䝹䝁䝃䝭䞁㻔㻳㼘㼏㻺㻭㼏㻕䛸䜾䝹䜽䝻䞁㓟㻔㻳㼘㼏㻭㻕䛜䚸
䃑䇲㻝㻘㻟 䛸䃑䇲㻝㻘㻠 ⤖ྜ䛷஺஫䛻㐃⤖䛧䛯 㻞 ⢾䝴䝙䝑䝖䛾⧞
䜚㏉䛧ᵓ㐀䛛䜙䛺䜛㧗ศᏊከ⢾䛷䛒䜚䚸≉䛻⤖ྜ⤌⧊䛾
⣽⬊እ䝬䝖䝸䝑䜽䝇ᡂศ䛸䛧䛶ᗈ䛟Ꮡᅾ䛧䛶䛔䜛䚹⣽⬊䛿䛣
䛾䝬䝖䝸䝑䜽䝇䛻䝠䜰䝹䝻䞁㓟 ཷᐜయ䜢௓䛧䛶᥋╔䛧䚸⣽
⬊ෆ᝟ሗఏ㐩⣔䜢άᛶ໬䛧䛶⣽⬊ቑṪ䜔⛣ື䛾ㄪ⠇
䛻ാ䛟䛸䛥䜜䜛䠄ᅗ䠍䠅䚹⚾㐩䛿䚸ୡ⏺䛻ඛ㥑䛡䛶䚸ື≀䛾
䝠䜰䝹䝻䞁㓟ྜᡂ㓝⣲䜢ぢฟ䛧䚸䝠䜰䝹䝻䞁㓟ྜᡂᶵᵓ
䛾ゎ᫂䛻ྲྀ䜚⤌䜣䛷䛝䛯䚹䛭䛧䛶䚸ྜᡂ㓝⣲㑇ఏᏊ⤌᥮
䛘䝍䞁䝟䜽㉁䜢⏝䛔䛯ヨ㦂⟶ෆ䝠䜰䝹䝻䞁㓟ྜᡂ䝅䝇䝔
䝮䛾㛤Ⓨ䛻ᡂຌ䛧䚸㓝⣲䜢άᛶ໬䛩䜛໬ྜ≀䛾᥈⣴䜢
ጞ䜑䛶䛔䜛䚹௒ᚋ䚸䝠䜰䝹䝻䞁㓟⏕ྜᡂᶵᵓ䛾඲ᐜゎ᫂
䛻ྲྀ䜚⤌䜏䚸䛭䛾◊✲䜢㏻䛨䛶䚸䜰䞁䝏䜶䜲䝆䞁䜾䜈䛾ᢏ
⾡ᒎ㛤䜢┠ᣦ䛩䚹㻌
㻌
䠍䠉䠎䠖⒴ᚤᑠ⎔ቃᙧᡂ䛾ศᏊᶵᵓ䛸⒴ᖿ⣽⬊䝙䝑䝏䜢
ᶆⓗ䛸䛧䛯἞⒪䛾ᇶ┙◊✲㻌
㧗㱋 ໬♫఍䛾฿᮶䛻䜘䛳䛶䚸ᡃ 䛜ᅜ䛷䛿䚸⒴䛜୺ 䛺
Ṛᅉ䛸䛺䜚䚸䛭䛾ඞ᭹䛜♫఍ⓗせㄳ䛸䛺䛳䛶䛔䜛䚹⒴䛿䚸
⏕࿨䝅䝇䝔䝮䛾⢭ᕦ䛺䝁䞁䝖䝻䞊䝹䜢㐓⬺䛧䛶⣽⬊䛜ቑ
䛘⥆䛡䜛䛣䛸䛷Ⓨ⑕䛩䜛䛜䚸⒴䛾㐍ᒎ䚸㌿⛣䚸෌Ⓨ䛾ṇ
☜䛺ᶵᵓ䛻䛴䛔䛶䛿䚸ᮍ䛰༑ศ䛺ゎ᫂䛜䛺䛥䜜䛶䛔䛺䛔䚹
㏆ᖺ䚸ከ䛟䛾⒴䛻䛚䛔䛶䚸䛂⒴ᖿ⣽⬊䛃䛾Ꮡᅾ䛜ሗ࿌䛥䜜
䛶䛚䜚䚸䛣䛾⣽⬊䛜⒴䛾※䛷䛒䜛䛸䛔䛖⪃䛘䛻ὀ┠䛜㞟䜎
䛳䛶䛔䜛䚹⒴ᖿ⣽⬊䛿䚸ᚑ᮶䛾໬Ꮫ⒪ἲ䜔ᨺᑕ⥺἞⒪
䛻᢬ᢠᛶ䜢♧䛩䛣䛸䛛䜙䚸㌿⛣䜔෌Ⓨ䜢ᘬ䛝㉳䛣䛩᭱኱
ᅗ䠍䠊䝠䜰䝹䝻䞁㓟ྜᡂ䛸䝅䜾䝘䝹ఏ㐩
㻌
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
㻌 ᡃ䚻䛿䛣䜜䜎䛷䛻䚸䝠䜰䝹䝻䞁㓟䜢㐣๫⏘⏕䛩䜛ங⒴
Ⓨ⑕䝰䝕䝹䝬䜴䝇䜢స〇䛧䚸ங⒴䛻䛚䛡䜛䝠䜰䝹䝻䞁㓟
⏘⏕䛾ቑຍ䛜䚸ங⒴䛾㐍ᒎ䜢ຍ㏿䛩䜛䛣䛸䜢᫂䜙䛛䛻䛧
䛶䛝䛯䚹䛣䛾⤖ᯝ䛻ᇶ䛵䛔䛶䚸⒴⣽⬊䛻䛚䛡䜛䝠䜰䝹䝻䞁
㓟䛾㐣๫䛺⏘⏕䛜䚸⒴Ⓨ⏕㐣⛬䛻䛚䛔䛶䚸⒴ᖿ⣽⬊䜢
ቑᖜ䛧䛶⒴㐍ᒎ䜢ಁ㐍䛩䜛䛸䛔䛖௬ㄝ䜢❧䛶䚸䛭䛾ド᫂
䜢⾜䛳䛯䚹䝠䜰䝹䝻䞁㓟䜢㐣๫⏘⏕䛩䜛ங⒴Ⓨ⑕䝰䝕䝹
䝬䜴䝇䛸ᑐ↷䝬䜴䝇䛻Ⓨ⏕䛧䛯ங⒴䛛䜙ங⒴⣽⬊䜢ᶞ❧
䛧䚸⣽⬊⾲㠃䛻䛚䛡䜛 CD44 䛸 CD24 䛾Ⓨ⌧䛻䛴䛔䛶
FACS ゎᯒ䜢⾜䛳䛯䚹䛭䛧䛶䚸䝠䜰䝹䝻䞁㓟䜢㐣๫⏘⏕䛩
䜛ங⒴䛷䛿䚸ᑐ↷䛻ẚ䛧䛶 CD44high /CD24 low ⒴ᖿ⣽⬊
ᵝ⣽⬊䛜ቑᖜ䛧䛶䛔䜛䛣䛸䜢᫂䜙䛛䛻䛧䛯䠄ᅗ䠎䠅䚹䛥䜙䛻䚸
Hoechst 33342 Ⰽ⣲䛾᤼㝖⬟䜢ᣦᶆ䛻 Side population
(SP)⣽⬊䛸㠀 SP ⣽⬊䜢ศ㞳䛧䛯䚹FACS ゎᯒ䛾⤖ᯝ䚸䝠
䜰 䝹 䝻 䞁 㓟 㐣 ๫ ⏘ ⏕ ங ⒴ ⏤ ᮶ 䛾 SP ⣽ ⬊ ୰ 䛻 䛿 䚸
CD44 high /CD24 low ⒴ᖿ⣽⬊ᵝ⣽⬊䛜⃰⦰䛥䜜䛶䛔䜛䛣䛸
䜢᫂䜙䛛䛻䛧䛯䚹䜎䛯䚸䝠䜰䝹䝻䞁㓟㐣๫⏘⏕ங⒴⏤᮶䛾
eradication of cancer has become a social mission.
SP ⣽⬊䛿䚸mammosphere ᙧᡂ⬟䜔㐀⭘⒆⬟䛸䛔䛳䛯⒴
Although it is well known that uncontrolled cell
ᖿ⣽⬊䛾≉ᚩ䜢♧䛩䛣䛸䜢᫂䜙䛛䛻䛧䛯䚹㻌
proliferation leads to the development of cancers, the
precise
䝠䜰䝹䝻䞁㓟
㐣๫⏘⏕ங⒴
ᑐ↷ங⒴
mechanisms
underlying
metastatic
tumor
progression and recurrence have not been fully resolved.
⒴
⒴ᖿ⣽⬊
Cancer stem cells (CSCs) have recently been reported to
exist
in
many
malignancies
and
have
attracted
remarkable attention because they are believed to be the
only cells capable of initiating cancer growth. Because
CSCs
are
relatively
resistant
to
conventional
chemotherapy and radiotherapy, and because they are
closely associated with cancer metastasis and recurrence,
ᅗ䠎䠊䝠䜰䝹䝻䞁㓟㐣๫⏘⏕ங⒴䛻䛚䛡䜛⒴ᖿ⣽⬊䛾
ቑᖜ
CSCs, like normal stem cells, reside and maintain their
㸱㸬Research projects and annual reports
stemness within a specialized microenvironment called a
1-1. Elucidation of the Biosynthetic Process of
Hyaluronan
and
its
targeting them is now a primary goal in cancer therapy.
Application
to
Anti-aging
stem cell niche. Thus, strategies to limit their stemness
and malignant transformation must focus on the
Technologies
importance of targeting this CSC niche. The main
There are an increasing number of bedridden elderly
purpose of our research in this domain is to identify the
people in Japan with a loss of joint function due to
cellular and molecular cues that govern the formation of
conditions like osteoarthritis. Hyaluronan (HA) acts as a
the specialized CSC niche microenvironment and
cushion and lubricant in articulating joints. It is an
establish novel therapies to induce a state of cancer
integral component of the synovial fluid between joints,
dormancy by controlling the niche.
but becomes reduced by age and thereby causes
functional disorders. HA is a high molecular-mass
2. Our previous studies using a hyaluronan synthase 2
polysaccharide
matrix,
(Has2) transgenic mouse model demonstrated that
especially of that of connective tissues, and is composed
hyaluronan overproduction by cancer cells caused rapid
of
development of aggressive breast carcinoma at a high
repeating
found
in the
disaccharide
extracellular
units
in
which
N-acetylglucosamine (GlcNAc) and glucuronic acid
incidence.
(GlcUA) are linked together by alternating ß-1,3 and
overexpression and hyaluronan overproduction may
ß-1,4 linkages (Figure 1). Our laboratory discovered the
accelerate
first mammalian HA synthase (HAS) gene and has been
subpopulations during cancer development. Primary
thoroughly
HA
cancer cells were established from mammary tumors
biosynthesis ever since. Recently, we succeeded in
developed in transgenic mice and subjected to the flow
establishing an in vitro reconstitution system using a
cytometric
investigating
the
mechanism
of
Thus,
cancer
we
hypothesize
progression
analysis.
Flow
that
Has2
by expanding CSC
cytometric
analysis
recombinant HAS protein and developed a screening
demonstrated
system for compounds that have HAS activation
CSC-like cells in Has2-overexpressing cancer cells
potential. Our future challenge is therefore to understand
(Figure 2). Hoechst 33342 dye exclusion assay was then
the entire mechanism of HA biosynthesis and apply this
performed to sort side population (SP) from non-side
knowledge
population
to
developing
innovative
anti-aging
technologies.
the
enrichment
(non-SP)
Has2-overexpressing
of
CD44
high
/CD24 low
cells.
The
SP
cancer
cells
contained
fraction
of
more
CD44high /CD24 low CSC-like cells than that of control
1-2. Studies on Cancer Microenvironment Formation and
cells. We found that this subpopulation exhibited several
the Establishment of Therapies Targeting Cancer Stem
characteristics that were similar to CSCs, including
Cell Niches
cancer-initiating and mammosphere-forming abilities.
Cancer has become the leading cause of death in our
㻌
country due to increased longevity, and as such the
䠐䠊ㄽᩥ䠈ⴭ᭩䛺䛹㻌
䠏䠅㻌 Ꮫእάື㻌 ᯈ㔝┤ᶞ䠖㻌᪥ ᮏ⏕໬Ꮫ఍ホ㆟ဨ㻌
᪥ᮏ⢾㉁Ꮫ఍ホ㆟ဨ㻌
P. Ontong, Y. Hatada, S. Taniguchi, I. Kakizaki, N. Itano: Effect
᪥ᮏ⤖ྜ⤌⧊Ꮫ఍ホ㆟ጤဨ 㻌
of a cholesterol-rich lipid environment on the enzymatic
activity of reconstituted hyaluronan synthase. Biochem.
᪥ᮏ䛜䜣㌿⛣Ꮫ఍ホ㆟ጤဨ 㻌
Biophys. Res. Commun. 443, 666-671
䝥䝻䝔䜸䜾䝸䜹䞁䝣䜷䞊䝷䝮ୡヰே 㻌
᪥ᮏᏛ⾡᣺⯆఍㻌
Y. Kashima, M. Takahashi, Y. Shiba, N. Itano, A. Izawa, J.
⛉Ꮫ◊✲㈝ጤဨ఍ᑓ㛛ጤဨ㻌
Koyama, J. Nakayama, S. Taniguchi, K. Kimata, U. Ikeda:
㻌
Crucial role of hyaluronan in neointimal formation after
vascular injury. PLoS One. 8, e58760
T. Ikuta, Y. Kobayashi, M. Kitazawa, K. Shiizaki, N. Itano, T.
䠐䠅㻌 ཷ㈹➼㻌 䛺䛧㻌
㻌
Noda, S. Pettersson, L. Poellinger, Y. Fujii-Kuriyama, S.
䠑䠅㻌 䛭䛾௚㻌 㻌
Taniguchi, K. Kawajiri: ASC-associated inflammation
ᒸᒣ኱Ꮫᖹᡂ 㻞㻡 ᖺᗘ་Ꮫ◊✲䜲䞁䝍䞊䞁䝅䝑䝥Ꮫ⏕䛾ཷ䛡ධ
promotes cecal tumorigenesis in aryl hydrocarbon
䜜䛸ᣦᑟ䚸ᖹᡂ 㻞㻡 ᖺ 㻥 ᭶ 㻞 ᪥䡚㻝㻝 ᭶ 㻞㻥 ᪥㻌
receptor-deficient mice. Carcinogenesis. 34, 1620-1627
䝩䞊䝮䝨䞊䝆䠖㻌
ᮃ᭶ಙ฼䠈ᯈ㔝┤ᶞ䠖䠉⢾㙐䛸⑌ᝈ䇲㻌 ⒴㐍ᒎ䛻䛚䛡䜛䝠䜰䝹䝻䞁
㓟⭘⒆ᚤᑠ⎔ቃ䛾ᙺ๭䠊 ⑓⌮䛸⮫ᗋ 㻌 31, 875-882㻌 (⥲ㄝ)
㼔㼠㼠㼜㻦㻛㻛㼣㼣㼣㻚㼏㼏㻚㼗㼥㼛㼠㼛㻙㼟㼡㻚㼍㼏㻚㼖㼜㻛㼪㼕㼠㼍㼚㼛㼚㻛㼕㼚㼐㼑㼤㻞㻚㼔㼠㼙㼘㻌
㻌
㻌
䠑䠊Ꮫ఍Ⓨ⾲䛺䛹㻌
N. Itano: Impact of the hyaluronan-rich tumor microenvironment
on cancer progression. International Society for Hyaluronan
Sciences 9th International Conference (Hyaluronan 2013),
Oklahoma City, OK, USA 2013.7.6㻌 (ᣍᚅㅮ₇)
T. Chanmee, K. Konno, P. Kongtawelert, N. Itano:
Hyperproduction of hyaluronan generate cancer stem-like cells.
International Society for Hyaluronan Sciences 9th International
Conference (Hyaluronan 2013), Oklahoma City, OK, USA
2013.7.7
◊✲ᐊ䝯䞁䝞䞊㻌
T. Chanmee, N. Itano: Hyaluronan production regulates
self-renewal of cancer stem cells. ➨22ᅇ᪥ᮏ䛜䜣㌿⛣Ꮫ఍
㻌
Ꮫ⾡㞟఍䞉⥲఍䠈ᯇᮏᕷ䠈2013.7.11
㻌
ᯈ㔝┤ᶞ: 䝠䜰䝹䝻䞁㓟ྜᡂ␗ᖖ䛸⒴䛾㐍ᒎ . ➨32ᅇ᪥ᮏ⢾㉁
Ꮫ఍ᖺ఍䠈኱㜰ᕷ䠈2013.8.6㻌 䠄䝅䞁䝫䝆䜴䝮䠅
㻌
䠒䠊䛭䛾௚≉グ஦㡯㻌
䠍䠅㻌 እ㒊㈨㔠
⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ᇶ┙◊✲䠄㻯䠅㻌
ㄢ㢟ྡ䠖䛜䜣⣽⬊ 䛾㐠࿨Ỵ ᐃ䛻ാ䛟Ὲ ửᅽ䛾⮬ᕫᙧ ᡂ䛸ᅇ
㑊䛾ᶵᵓ㻌
◊✲௦⾲⪅䠖ᯈ㔝┤ᶞ㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻟㻙㻞㻡 ᖺ㻌 㻔㻟 ᖺ㻕㻌
ඹྠ◊✲⤒㈝䠄㻿㻮㻵 䝣䜯䞊䝬ᰴᘧ఍♫䠅㻌
ㄢ㢟ྡ䠖㻡㻙䜰䝭䝜䝺䝤䝸䞁㓟䠄㻡㻙㻭㻸㻭䠅䛜ྛ✀ᇵ㣴⣽⬊䛾⣽⬊
እ䝬䝖䝸䝑䜽䝇ᵓ⠏䜈ཬ䜌䛩ᙳ㡪䛻䛴䛔䛶䛾◊✲ 㻌
◊✲௦⾲⪅䠖ᯈ㔝┤ᶞ㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻞㻙㻞㻢 ᖺ㻌 㻔㻡 ᖺ㻕㻌
㻌
䠎䠅㻌 ▱㈈ᶒ➼㻌 䛺䛧㻌
㻌
043,"2)+.*1-/$ $
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džǕǀƺǩƹǕƻƼØĽǙ.]Á¼ǥÛÕ_æ‹ďǬݨLjƵ
Ų yîöcǔǚƵ¢ǍǗîö.ŞƸ?ŏšǙ.]ÛÕ
ĐIJǼȎȤȇǙ€ķ ǀƵĘæǘ¢ÛȀȢȍǵŃǙƸŕE
_ƹǙţ–ǕŔǬĤǐǓƻǩƶÛEÌ3Ǭ•ƼȀȢȍǵŃǚƵ
Ç`ƹǬŔLjǓƻǩ=Ĕ†ǬŌÆljǩƶdžǙǦƼǗHًĺ
ƉƓƆ ǘ®ǁʼnǡǪƵƨƖƓƆŲ ǘ+Lj;ǧǪǍ؉Qǘ}ǐ
ǙǔƵĄēǘ¤DŽǩ?ŏšȥ±ǎ ƮƖƓƆ .]ǘć?Lj
ǍŬàǔǭȖȋŜǀŬÂć?ljǩdžǕǘǦǐǓǧǪǩƶdžǙ
ǓƻǩȔȞȒȑȁȇšȦǘËéLjǍîöǬiţLjǓƻǩƶŲ
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ƸĐIJƹǚǾȢȆȝȟȇǶȕǙǴȤǕǗǩŖôǔƺǨƵȞȓǿȤȗ
ǘƾƻǓȅǹȤȅǮȢǶȥ‰Q,ÙȦǕȒȑȁȇć?zȥǷ
86
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ǘƾƻǓۏLJǪǩ?ŏšȥƫƪƧƱƫơƫƮƥƠƱƧŸƮƖƓƆȦǚƵ
ĔǙݵȮŲ ·ĞğǙ ƒƥƢƒ ǚĖĿŐŚ/ǕǗǩâņŭO
ȆȢȊȟǬŐǐǓȞȓǿȤȗǙWǘ-ǓĤǂƶŲ
ǬȲ²øǘǤǏƵĖȀȢȍǵŃǬĖǘš%LJNjǩ ƛƥƠƈ ĆŅǘ
Ų ƷǚƵdžǪǧǙŖôǀƵÁºæǔ6ķǗǤǙǔǚǗǂƵȞ
ǦǐǓĖǘš%LJǪǩƶ·Ğğǘ^NljǩǑǙ ƛƥƠƈ L]
ȓǿȤȗǕ?ŏšǀëÜLjǑǑƵċ…Ǚ1Ǭ
ǙƼǏƵƗƫƪƎƎƎƏ ǀĬǗL]ǕLjǓ"ƻǓƻǩǀƵƗƫƪƎƎƎƏ Ǚ
ǐǓŔĤljǩǤǙǔƺǩdžǕǬðLjƵËéLjǓƻǩƶƸ?ŏ
̆ǀljǩǕƵùȩǙL]ǔƺǩ ƛƥƠƈŽ ǀĵfLJǪǓ"
ǔ"ǂƹǕƻƼƵȀȢȍǵŃǙ¢ǍǗƺǨ£ǤĭƻǎLjǍƶ)
ǂƶƒƥƢƒ ǚ ƛƥƠƈ ĆŅǙ̆ǬșȉȀȤLjǓƵ̆«ǘ
æǘǚƵȀȢȍǵŃǙĄēĦjǞǙhN4ǬçĮLjǓĖ
ƛƥƠƈŽ ǙĐIJǬĵfljǩ1L]ǔƺǨƵ
Ř]Ǚ
ŎŖŰ3L] ƗơƟƆ ǙãØ1ǬĤƼYĕğ ƗơƟƒ ǥƵĖȀ
Í ƔƖƋ ǘǦǐǓǹȤȇLJǪǩƶȱȷȶȱǙ ƈ ²øŊǂǘǚȞȓǿ
ȢȍǵŃǙĄēĖǞǙš%ŖôǬçĮLjǓĖš%ħč
ȤȗȆȢȊȟǕëÜljǩdžǕǘǦǐǓėǧǙĐIJŢǭȠ
ƛƥƠƈ ǙĐIJ1ǬĤƼ·Ğğ ƒƥƢƒ ǗǖǬǕǨƺDžǓƻǩƶŲ
ǼȆǬxǁńdžljǭȖȋŜŚ/ȥǭȠǼȆŚ/ȦǀƺǩƶdžǙŢ
Ų ƖơƣƯƧƝƮƪƬƱŲ ƩƝƭƟơƩƮŲ ƫƪƧƱƫơƫƮƥƠơ ǕDǛǪǩdžǪǧǙșȉȀ
ǭȠǼȆǚœĈLjǍȫǑǙǹȇȢǔīŸKČǨŋLJǪǩƶdžǙ
ȤȀȢȍǵŃǚȞȓǿȤȗȆȢȊȟǙ.ǕëÜLjǓĐIJ
ŤƵ÷ǏÃǡǐǍȞȓǿȤȗǘǦǐǓ ƨƖƓƆ Ǚ¼ŒǀǠ
ǘȐȠȤǴǬƿDŽǩƸǭȠǼȆŚ/ƹǬ˜Ǒ£ƵȲ²øŊǂ
ǃǪƵÍŘ]
ǙĐIJǀ=ĔǕǗǩƶljǗǫǏƵǭȠ
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ǼȆǙ«ŤǀŢƻǠǖ ƛƥƠƈŽ ǙãØşǀ§ljǩƶǭȠǼȆ
ǪǧǙ̆ǘD„LjǓĐIJǘȐȠȤǴǬƿDŽǩ«ŤǬÇǣǓ
ǚ ƒƥƢƒ ?ŏšǀ ƗƫƪƎƎƎƏ ǘǦǩĖąʼnǢ:„Ǭ<DŽǩǕ
ƻǩƶdžǙǦƼǘ ƨƖƓƆ ǔǙȞȓǿȤȗǙ3ǁǀ1LJǪƵ
İŧLJǪǩǍǣƵƗƫƪƎƎƎƏ ̆Ǖ ƛƥƠƈŽ ãØşǀōëťǬð
ƨƖƓƆ .]Ǚ׌V4Ǖ¾æŘ]ǙĐIJ1ǀĤǫǪǩƶ
ljƶdžǙȏǮȤȇȌȂǵÁ¼ǬaűȃȤȟǕLjǓ0ÜljǩǕƵ
ǡǍĐIJǼȎȤȇǙċ…1ǚƵ¢ÛȔȞȒȑȁȇšǙȏDz
êœæǗÏ`ǀMũǗĄē*Ǚ ƗƫƪƎƎƎƏŲ ŵƛƥƠƈŶŲ Ǚ̆ǬƵ
ȤȟȅǮȢǶǥhN4ǗǖǙƸÓȑȡǾǼƹǀæïǘńdžǩ
ƑƝƟƜ śĂ̆ƿǧd©ǘƵƿǑ`şæǘĭõǤǩdžǕǀǔǁ
ǍǣǙŝĬǗĬĂǔǚǗƻƿǕđƽǓƻǩƶŲ
ǩƶdžǙǦƼǗȠȔȤȀȤǔƺǩŲ ŴŸ ǬÌÜLj
Ų ƗơƟƒ ǥ ƒƥƢƒ ǙãĭǘǦǨðLjǍƸĐIJǙǼȎȤȇǀƵ?
ǓƵƛƥƠƈ ȀȢȍǵŃǙ¼ŒǕÁĔǙĴĄǗݵǬŔǣǓƻǩƶ
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ŦY_RnîöcǗǖǕǙ(AîöǘǦǨƵ¢ǍǘÇ`LJǪ
Ǎ ƛƥƠƈ Ǚć¬¼ŒǘPǒǂÁĔݵǬĤǐǍƶnjǙć¶Ƶ
ƛƥƠƈ Ǚ̆ǘŝĬǗǭȖȋŜÄPǬA`LjǍƶnjLjǓƵƛƥƠƈ
ǚȔȞȒȑȁȇŎŖȁȚȊȟǘǦǧNJƵĖ*řǘįņÚT
ǬǨ-ljdžǕǘǦǐǓƵȀȢȍǵŃǙĖąʼnǢǬŔljǩǕ
ǙƵ¢ǍǗȘdzȉǽȗǬžGLjǍƶŲ
Ų
ŽŶŲ ĐIJǭȠǼȆǙİŧÁ¼ȮŲ ĐIJŢǭȠǼȆǬńdžljdžǕ
ǘǦǐǓȀȢȍǵŃ.ÈŰ3L] ƗơƟƆ ǙĐIJķþǬĤƼ
ƗơƟƒ ǚƵnjǪėņǻǶȈȟŚ/ǬǤǑ.ÈȀȢȍǵŃǔƺǨƵ
njǙ?ŏšǀ ƗơƟ ħčǘǦǩĖŎŖ:„Ǭ<DŽǩǕǭȠ
ǼȆǀİŧLJǪǩǕƻƼȏǮȤȇȌȂǵ1Ǭ<DŽǩƶƗơƟƒ Ǚ
This year’s accomplishments:
ĐIJǭȠǼȆǀĖŎŖ:„ǘƻİŧLJǪǩÁ¼ǘƵƗơƟƒ
1. Analysis of the membrane protein insertase YidC using
?ŏšǙƼǏƵȞȓǿȤȗǙWǔȞȓǿȤȗǘŊœLjǍř
MifM. YidC is an evolutionarily conserved membrane protein
ǘƺǩ żŻ ÄPǙǭȖȋŜŚ/ǀ‚ĬǕLJǪǩdžǕǬĭ-Lj
that facilitates insertion of a class of cellular proteins into the
ǍƶǭȠǼȆǙ1ǘǚǻǶȈȟŚ/ǕǭȠǼȆŚ/Wǘ
membrane. B. subtilis MifM up-regulates translation of the
ƗơƟƒ ǙZŭOǀťljǩdžǕǀ¨ǧƿǕǗǐǍƶŲ
cis-located target gene that encodes a YidC homolog (YidC2)
by undergoing translational elongation arrest. This system
ȮŲ ĐIJŢǘƾDŽǩÎő
operates when the activity of the main YidC homolog is
ǥ«!ÃǀǖǙôvĘæǘńdžǐǓƻǩǙƿǬ¨ǧƿ
lowered. We used this MifM-mediated YidC monitoring
ǘljǩǍǣƵ?ŏšȥƳƩƝƭƟơƩƮƪƨơƴǕDǝdžǕǬžGȦǀ
mechanism as a research tool. A lacZ translational fusion,
²øǘ(¯ć?ǔœćLjǍ ƮƖƓƆ ǬǤǑdžǕǬ0ÜLjǍaű
mifM-yidC2'-lacZ, can report the cellular activity of the YidC
£ÉǬţãLjƵĊĎæݵǬĤǐǓƻǩƶ¥ǘƵYĕğǙŘ
pathway, which otherwise is difficult to assess directly. In
] żŷŻŻŻ
ǙĐIJǬƵȍȟǼȁDZǯǼ ƥƩŲưƥưƪ aűǕĀ
collaboration with the Nureki (University of Tokyo) and the
ĪL]ǬÜƻǩ ƥƩŲưƥƮƬƪ ĐIJaűǔA«ĤæǘķǟǍƶnj
Tsukazaki (Nara Institute of Science and Technology)
Ǚć¶ƵXǂǙȀȢȍǵŃǙ?ǀ?ı ſŻŻŻ ý’Ŋǂǘ9
laboratories, we carried out functional dissection of YidC that
ǝřǔÎőljǩǕƻƼŠWǙaǀ¨ǧƿǘǗǐǍƶƎƩŲ
was based on its newly solved crystal structure. Our results
ưƥưƪ Ǖ ƥƩŲ ưƥƮƬƪ ǔǙŗƻǥ(ՆƿǧnjǪǧǬ.ůLjƵĐIJ
suggest that YidC mediates membrane protein insertion by
ÎőǙ8LǬ›ǐǓƻǩƶŲ
providing a hydrophilic platform within the membrane interior,
Ų
instead of forming a polypeptide-conducting channel.
žŽ
ſŶŲ ÔǻȜȂǵŇ+L]Ʋ Ǚ1Á¼ȮŲ bFîöFǙÞę
2. Arrest release mechanisms of SecM. E. coli SecM is a
7UǀǕǗǐǍ¦ÿ(AîöǘǦǨƵYĕğǘƾƻǓÔ
secretory protein encoded by an upstream open reading frame
ǻȜȂǵȥǼȆȠǼȦ„üŘ]ǙŇ+Ǭ>ǩƲžŽŲ ȀȢȍǵŃǀƵ
of secA. It controls the expression of SecA, the export-driving
ƗƖƕ ĆŅǘǦǐǓĄēĖǘhN4ljǩdžǕƵnjǙdžǕǀȀȢȍ
ATPase, by undergoing translational elongation arrest, which
ǵчq†ȥƫƬƪƮơƪƭƮƝƭƥƭȦǙĉ˜ǘŝĬǔƺǩdžǕǬĭ-Lj
is in turn subject to export-coupled release. We found that a
ǍƶŲ
sequence of 10 amino acids, which resides just upstream of the
polypeptide region embraced by the exit port of the ribosome,
Research projects and annual reports
participates in the event of arrest release. Thus, not only the
We intend to develop a new area of research, which
signal peptide and the arrest motif but also the segment
might be called “nascent chain biology” by addressing a
flanked by them is important for the regulatory function of
concept that translation elongation speed is fine-tuned by
SecM.
intra-ribosomal part of amino acid sequences of the translation
product
as
well
as
by
dynamic
behaviors
the
We examined the generality of the occurrence of translational
We found
pausing by detecting nascent chain intermediates in the
that some of cellular factors that facilitate secretory protein
biosynthesis of E. coli proteins, using methods based on the
export and membrane protein insertion are controlled by
presence of a covalently attached tRNA at the end of each
regulatory nascent polypeptides that function in accordance
nascent chain. Combined approaches by in vivo pulse-chase
with this principle. We are studying molecular mechanisms
labeling and cell-free translation revealed that a majority of
and physiological outcomes of the regulation.
extra-ribosomal part of the same nascent chain.
of
3. Profiling translational elongation of E. coli proteins.
Also, we have
the ~1,000 proteins examined underwent one or multiple
developed experimental methods that enable us to study
events of pausing either in vitro, in vivo or both. A variety of
cellular polypeptidyl-tRNAs, obligatory but poorly studied
mechanisms can be considered that account for the pausing
intermediates in translation, which we proposed to call
and we are in the process of elucidating them.
collectively "a nascentome". We are combining these
4. Involvement of membrane localization in the
approaches to uncover still unknown principles and details
regulation of the heat shock transcription factor σ32. A
that accompany the processes of genetic information
collaborative study coordinated by Dr. Yura, a prominent
transformation into biological outputs.
guest scientist in this laboratory, revealed that the transcription
factor σ32 of E. coli is localized to the cytoplasmic membrane.
This unexpected property of σ32 has been shown to be
7tƅŲ řÖáæ ƥƩŲưƥưƪ $¸ÀÉǘǦǩȀȢȍǵŃĖŎŖŔ
important for the feedback regulation of its activity and, hence,
L] ƗơƟƉƋ ǙPŃć?řǙ›ăŹŲ ù żŻ KŲ ŽżŲ āYĕğî
for the maintenance of proteostasis both in the cytosol and the
öŷŲ ŪlìIeŷŲŽŻżžŹŲƁŹŲŽŻŸŽżŲ
membrane. ƈƤƝƠƝƩƥŷŲƛŹŷŲƈƤƥƞƝŷŲƗŹŲƝƩƠŲƎƮƪŷŲƐŹŲƕƬƪƢƧƥƩƣŲƫƪƧƱƫơƫƮƥƠƱƧŸƮƖƓƆƭŲƮƪŲ
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96!5'&$
Kumazaki, K*., Chiba, S*., Takemoto, M., Furukawa, A., Nishiyama,
ƈƪƩƢơƬơƩƟơŲŽŻżžŷŲƓƝƫƝŲƚƝƧƧơƱŷŲƈƝƧƥƢƪƬƩƥƝŷŲƙƗƆŷŲƏƯƧƱŲƄŸżŽŷŲŽŻżžŲ
ƈƤƥƞƝŷŲƗŹŲƝƩƠŲƎƮƪŷŲƐŹƅŲƒƥƢƒŲƥƩƠƯƟơƭŲƨƯƧƮƥƭƥƮơŲƬƥƞƪƭƪƨơŲƭƮƝƧƧƥƩƣŲƥƩŲ
K., Sugano, Y., Mori, T., Dohmae, N., Hirata, K., Nakada-Nakura,
ƨƪƩƥƮƪƬƥƩƣŲƨơƨƞƬƝƩơŲƫƬƪƮơƥƩŲƞƥƪƣơƩơƭƥƭŹŲƖƥƞƪƭƪƨơƭŲƈƪƩƢơƬơƩƟơŲ
Y., Maturana, A.D., Tanaka, Y., Mori, H., Sugita, Y., Arisaka, F.,
ŽŻżžŷŲƓƝƫƝŲƚƝƧƧơƱŷŲƈƝƧƥƢƪƬƩƥƝŷŲƙƗƆŷŲƏƯƧƱŲƄŸżŽŷŲŽŻżžŲ
Ito, K., Ishitani, R., Tsukazaki, T. and Nureki, O. (2014) Structural
ƈƤƝƠƝƩƥŷŲƛŹŷŲƔƩƪŷŲƐŹŷŲƎƮƪŷŲƐŹŷŲƐƯƭƯƦƝƦơŷŲƐŹŲƝƩƠŲƆƞƪŷŲƘŹƅŲƆƬƢƆŲ
basis for Sec-independent membrane protein insertion by YidC.
ŵƛƤƠƑŶźƖƋŽŲƝƩƠŲƆƬƢƇŲŵƛƝơƏŶŸƨơƠƥƝƮơƠŲƝƧƮơƬƩƝƮƥươŲƬƥƞƪƭƪƨơŲ
Nature, in press (*These authors contributed equally to this work)
ƬơƭƟƯơŲƭƱƭƮơƨƭŲƥƩŲƊƭƟƤơƬƥƟƤƥƝŲƟƪƧƥŹŲƖƥƞƪƭƪƨơƭŲƈƪƩƢơƬơƩƟơŲŽŻżžŷŲ
ƓƝƫƝŲƚƝƧƧơƱŷŲƈƝƧƥƢƪƬƩƥƝŷŲƙƗƆŷŲƏƯƧƱŲƄŸżŽŷŲŽŻżžŲ
Mio, K., Tsukazaki, T., Mori, H., Kawata, M., Moriya, T., Sasaki, Y.,
Ishitani, R., Ito, K., Nureki, O. and Sato, C. (2013) Conformational
5ġƒƵĢĉªƅŲ ĐIJǭȠǼȆǬLjǍ·Ğğ ƒƥƢƒ ǘǦǩģå
ŃĖąʼnL] ƛƥƠƈ Ǚ1ŹŲ ǶȝȗŨ†ğǸȋȗÁĔĻŷŲ ûÊŷŲ
variation of the translocon enhancing chaperone SecDF. J. Struct.
ŽŻżžŹŲƄŹŲƂŸƄŲ
Funct. Genomics, 10.1007/s10969-013-9168-4
Lim, B., Miyazaki, R., Neher, S., Siegele, D.A., Ito, K., Walter, P.,
5ġƒƵĢĉªƅŲ ·Ğğ ƒƥƢƒ ǚƵțȉȤǵǗĐIJǭȠǼȆǬ
Akiyama, Y*., Yura, T*. and Gross, C.A*. (2013) Heat shock
LjǓģåŃĖąʼnL]ǙãØşǬķþljǩŹŲ ù Ƃ KĄğ_Ĝ“
transcription factor σ32 co-opts the signal recognition particle to
ǹȡȂǾǰȗŷŲ umpŷŲŽŻżžŹŲƃŹŲƂŸƄŲ
regulate protein homeostasis in E. coli. PLoS Biol. 11(12),
ĝļˆrƵ5ġƒƵĢĉªƅŲ ?ŏšǙݵǘǦǩĐIJ
ŢŖôǙ&dݨǘCDŽǓŹŲ ù Ƃ KĄğ_Ĝ“ǹȡȂǾǰȗŷŲ u
e1001735. DOI: 10.1371/journal.pbio.1001735 (*Corresponding
mpŷŲŽŻżžŹŲƃŹŲƂŸƄŲ
authors)
Ito, K. and Chiba, S. (2013) Arrest peptides: cis-acting modulators of
ĝļˆrƵ5ġƒƵĢĉªƅŲ YĕğĐIJŏšǙĊĎæݵŹŲ
¦³Ř_ùŲ ȭȬKYŷŲ ŽďSYȣ¦@ǴȚȢȍǼŷŲŽŻżžŹŲ
translation. Annu. Rev. Biochem. 82, 171–202 (Review)
ƄŹŲżƄŸŽżŲ
Akiyama, Y., and Ito, K. (2013) HtpX peptidase. pp. 683-685,
Handbook of Proteolytic Enzymes 3rd ed. (ed. Rawlings, N. D.
and Salvesen, G.) Academic Press (Review)
;6%(
Hizukuri, Y., Ito, K., and Akiyama, Y. (2013) RseP Peptidase. pp.
#$
ȨȦŲ WřŁŠ
1545-1550, Handbook of Proteolytic Enzymes 3rd ed. (ed.
ò_îöŀĩ2ŠȣPèîöȥƇȦŲ Ų
Rawlings, N. D. and Salvesen, G.) Academic Press (Review)
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-T17, which were identified by us, are brain-specific and
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1) Analysis of mice defective of a GalNAc-T17 gene
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hippocampus and amygdala, but in ventromedial nucleus
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GalNAc-T17 may therefore positively regulate feeding
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2) Production of zebrafish GalNAc-T mutants
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GCƮºżƪǪŁŬŬŬłŀ ǣLjǐƳǥģƘ&žƓǪǐljLjǁƼǎ
ǢĭY$ƔŻƪ ŕŒŠţ Ʈ«&ƉƪǪŁŬŵłŀ
*ƙ"Œ¤
İƘ ŗŘŗŏ Ʈ«&ƉƪÖƙƮƕƩƫƍǫƌƙâ’Ǫ
To produce zebrafish mutants defective of GalNAc-T
genes, we employed recently developed genome-editing
technology, TALEN and CRISPR/Cas systems.
We
*Ċ\ĪQk Ŋŋ ˆÆƘÎáÓđƙivǪō ˆÆ
found that mutations were successfully introduced at the
ƘƚƧƩ¨ÃƗÓđgƁāZƆƫƍǫ¿”ñƥƸǢ
target sites in the zebrafish embryos using TALEN and
ǁƴǜƳǝǧǂǥƼƗƖƘƧƪÑƘƧƩǪō ˆÆƔïj
CRISPR/Cas vectors for GalNAc-T9 and -T18.
ÄƗÎá¨)Ʈ‹Ƈƍv±ÎáßéƝƙ
3) A rapid and efficient method for neuronal
*Ɓĉƣƨ
ƫƪ‡ƔǪƼǡƱßéƚUBƇƗƀƐƍǫƧƩǪ†
Ƈż‡¦ƔƚǪŠňŐ ßéƚmƙÝ+
(µƧƃÎáßéƘƙơ
induction of P19 embryonic carcinoma cell line
ƙŠīƔǪ
*ƉƪƅƕƁ‰ƨƀƕƗƐƍǫŀ
We revised a novel method to efficiently differentiate
P19 cells into neurons by an adherent culture in
ǯǩƌƙ
ƙşńƼǡƾǁǍEÛĨƙžêÑŀ
laminin-coated dish in the presence of several reagents to
ŀ ßéMƔöƉƪ†ÿ şńƼǡƾǁǍEÛĨƙžêƮǪ
induce neural differentiation and suppress growth of
DžǖǠǕƲljǁǟƮºżƓČƞƍǫwźƚƅƙÛĨœĚƙ
non-neural cells.
5vƘĬƭƪÛēÐĢÞƁ"ŒèƘſżƓëƘhƃÃ
within 4 days without gliogenesis.
¶ƉƪƅƕƮþżƎƇƍǫƠƍǪĢÞƙöƮ}#Ɖƪ
obtained were responsive to several neurotransmitters
ƕǪëƘſżƓit½cƮ¸ƈƪƙƘ[ƇǪ
ƙàäƔ
with functional neuronal networks.
ƙù ¶ E ƙL * ƚā Z ƆƫƗƀƐƍǫƅƙ ƀƨǪƅƙ
4) Analysis of extracellular O-glycosylation
ĢÞƁƘëƘſżƓžêƉƪƁÌ<Ɔƫƍǫŀ
The new method induced neurons
The mature neurons
We investigated the function of a glycosyltransferase
ŀ
in
Research projects and annual reports
O-glycosylation.
zebrafish,
which
catalyzes
extracellular
novel
We found that it was strongly
We have been investigating roles of O-linked sugar
expressed in the brain of zebrafish embryos, and its
chains with the linkage structures, GalNAcα1→Ser(Thr),
suppression caused alterations in the brain development.
Manα1→Ser(Thr),
or
GlcNAcβ1→Ser(Thr).
O-GalNAc-type sugar chains are called mucin-type
96532!
carbohydrates and their biosynthesis is initiated by a
Y. Nakayama, A. Wada, R. Inoue, K. Terasawa, I. Kimura, N.
group of enzymes, UDP-GalNAc: polypeptide N-acetyl-
Nakamura, A. Kurosaka: A Rapid and Efficient Method for
galactosaminyltransferases (GalNAc-Ts).
Neuronal Induction of the P19 Embryonic Carcinoma Cell Line.
GalNAc-Ts
consist of a large gene family with 20 isozymes in
humans.
Interestingly, GalNAc-T8, -T9, -T17, and
Journal of Neuroscience Methods, in press.
M. Ogawa, N. Nakamura, Y. Nakayama, A. Kurosaka, H. Manya,
ĿDŀ ǰˆ¸*VĆč;ǪˆõVė¾…ğR;ŀ
M. Kanagawa, T. Endo, K. Furukawa, T. Okajima: GTDC2
ŀ
modifies O-mannosylated ŷ-dystroglycan in the endoplasmic
Ǯǩŀ ƌƙ
ŀ
reticulum to generate N-acetyl-glucosamine epitopes reactive
ĿDŀ ǰśŢŤ ƿƳƶǥǃƾǧǃǨĠ¹›OVĮ_ľ–¸l
with CTD110.6 antibody. (2013) Biochem Biophys Res
Ƙ ŘŗŠ ƙöƕÚüXĽƮ÷ƐƍǫǩǨʼnŇňŊŅŎŅʼnōǩǫŀ
Commun 440(1), 88-93
ŀ
I. Kimura, Y. Nakayama, Y. Zhao, M. Konishi, N. Itoh:
Neurotrophic effects of neudesine in the central nervous system.
(2013) Front Neurosci 7 (article111), 1-5
Y. Nakayama, N. Nakamura, D. Tsuji, K. Itoh, A. Kurosaka:
Genetic diseases associated with protein glycosylation
disorders in mammals. pp. 244-269 in Genetic Disorders,
Maria Puiu (Ed.), ISBN: 978-953-51-08866-3, InTech.
ŀ
:632ŀ
a>‰, :»ŻƦơ, ŽÇ, ĿDǰ P19ǚƴǃèrì
Âßé—ƮºżƍĖęƀƑ(µƙðżÎáĊ\¦ƙËÔ.
Õ36?ˆ
T¸²VdǪÎybǪ2013.12.3-6
Y. Nakayama, K. Kato, N. Nakamura, A. Kurosaka: The roles
of a putative polypeptide GalNAc-transferase/Wbscr17.
International Symposium on Glyco-Neuroscience, Awaji city
(Japan) 2014.1.9-11
ŀ
;614!
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ćĸ=ˆ¯åêĶSato et al. Int. J. Mol. Sci. 2013ķ×ãõ
¹`ðöŠXÉ7@)G EGFR õ 845 †‹õėı
u> `npo 4H3B8 Y./1j^`ngl^odoi`7VY
ēijq<Ķėıēij 845ķõĮijÇ"ôzyćÚïÖèõĮ
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çÿõÖèåï „ ĖijĠĐ¼ ô' T U ć çÿõõ
$ƒu‚‹­Mjt
yw‚“/Žs„x|nEw…
identify a change(s) in the proteome compositions during
­™§©¨…7I›¨ ™`…"“]Š€pn‹
hormone-induced oocyte maturation and subsequent
q¬†mRU“B5‚3B5…„Pxm
sperm-induced egg activation.
z‘{‘sŽW£•™§Ÿ¤•¨“_Zx€›¨ ™`…
in the Egg Project include characterization of rat
monoclonal
antibodies
that
Other on-going subjects
were
raised
against
membrane proteins of unfertilized Xenopus eggs, live
cell-imaging of ATP in Xenopus oocytes and eggs by the
use
of
ATeam,
a
FRET-based
probe
for
ATP
visualization and quantification (in collaboration with
Drs. Ken Yokoyama and Jun-ichi Kishikawa, Kyoto
Sangyo
University;
Yasuhiro
Iwao,
Yamaguchi
University; and Hiromi Imamura, Kyoto University) and
& ! "!#
analysis of stomatin-like protein 2 as a newly identified
tyrosine kinase substrate that localizes to membrane
C+“;ay‚pqKNonw‘†”¡¥—œ
microdomains and mitochondria in Xenopus eggs (in
¤˜–¦…Q„rvQ
@tB5Y'„
collaboration with Drs. Hitoshi Sawada and Lixy
yw‚sŽm 5 …Y ' 6 c yƒ’}W ›¨ ™
Yamada, Nagoya University). In the study of human
` …S , „d pto…†ƒps‚pq ^ “O €m
bladder carcinoma cells, which we call Cancer Cell
z…4\“]Š‹…onw‘‰ 3,000 …
Project, we are now investigating phosphorylation state
RUª(„o0,A:RU«sŽ].“_Zxm
of the epidermal growth factor receptor/kinase (EGFR)
9i<>=„›¨ ™`…h‚£šš¢™
in 5637 cells that are cultured under serum-containing or
ž§¤ž¥[1“rwƒ~|ª%!!gF!KN
serum-deprived conditions. Results obtained demonstrate
L & X ? # k - ‚… K N «nz…T 2 m 5 …
that EGFR is tyrosine-phosphorylated in serum-deprived
Y ' 6 c yƒ’}W ›¨ ™` …S , „ b @ ‚J d
5637 cells, where sustained Src activation has been
@tow‚t/Žs‚ƒ~|ª­«n)†w…©›
shown to occur and to play an important role in the
“„x€m,A‡Q„qRUW£•™§Ÿ¤
anti-apoptotic growth of the cells under these culture
•¨… Q 8 V D * ŒH G e 8 6 ‚…f ’“_ ˆ
conditions. Our special interest is to determine the
€pu"on
occurrence of phosphorylation of Tyr-845 of the EGFR,
l
a Src-dependent phosphorylation site, and to evaluate its
Research projects and annual reports
Research in our laboratory focuses on the physiological
physiological function.
l
function of the tyrosine kinase Src and its interacting
'%$
signaling proteins in oocyte/egg of the African clawed
Sato, K.: Cellular functions regulated by phosphorylation of
frog Xenopus laevis and in human bladder carcinoma
EGFR on Tyr845. International Journal of Molecular Sciences
cells (e.g. 5637 cells). In the study of Xenopus
14, 10761-10790, 2013.
oocyte/egg, which we call Egg Project, we are currently
Ijiri, T.W., Vadnais, M.L., Huang, A.P., Lin, A.M., Levin, L.R.,
examining whether animal and vegetal hemispheres are
Buck, J., Gerton, G.L.: Thiol changes during epididymal
different with each other in their compositions of
maturation:
membrane-associated proteins. To this end, we have
spermatozoa? Andrology in press201312.
a
link
to
flagellar
angulation
in
mouse
prepared low density, detergent-insoluble membrane
Ijiri, T.W., Vadnais, M.L., Lin, A.M., Huang, A.P., Cao, W.,
fractions (membrane microdomains) from both animal
Merdiushev, T., Gerton, G.L.: Male mice express sperma-
and vegetal halves of immature ovarian Xenopus oocytes,
togenic cell-dpecific triosephosphate isomerase isozymes.
performed two-dimensional electrophoresis and mass
Molecular Reproduction and Development 80, 862-870, 2013.
spectrometry of proteins. Results obtained so far show
Sato, K., Mahbub Hasan, A.K.M., Ijiri, T.W.: Focused proteom-
that there are indeed common as well as distinct protein
ics on egg membrane microdomains to elucidate the cellular
compositions in these samples. Further study will aim to
and molecular mechanisms of fertilization in the frog Xenopus
laevis. In Sexual Reproduction of Animals and Plants in press.
¤
(Springer)
Ijiri, T.W., Kishikawa, J., Imamura, H., Iwao, Y., Yokoyama, K.,
Sato, K.: ATP imaging in Xenopus laevis oocytes. In Sexual
Reproduction of Animals and Plants in press. (Springer)
„ – : ÏÐìh d 1 íU 1 $ ® S ’ l Š ®Ñâ
ÝÐì}ŠJDî, 2013.
¤
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s1ov”ˆžëO1†¢)ovíovî¤
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j¼‚…#¾0\X¤
ov‡ò„–§¤ !EABò­ª«¨ª¬ A¤ ¥ª A¦¤
šiW.1O‰ovŽ£KHMLÝèÉåà¤
¤
Ž£%ò#3:;-..5
“®<?a®Tƒ®>4nu®œr®;7C
2<09¤
2®Y9®„–: ATP quantification and live-imaging in
Xenopus laevis oocyte. w36&PR0hd1AïpI
@ï2013.12.3-6
=
ov‡ò„–§¤ !EABò­ª¬ A¤ ¥© A¦¤
ñî¤ 1-áÕý³µ¿ovŒ¤
“®<?a®Tƒ®>4nu®œr®;7C
AB½k‡·¹1†NíIjiri et al. J. Signal Transd. 2012î
2 ®Y 9  ® „ – : ÂÛæÆÓáÇÅç ^ z € ½³µ¿
´ovÊßãØÔÃÌÄÖ Global Medical Discovery ¾ Key
ATP¾b3¼ATPåÄÜÄáìÎêÉ. w51&PRhdd
Scientific Articles ¾ º ¼ · » { ¶ À ¹ ¯
g1Aïš@ï2013.10.28-30
URL:http://globalmedicaldiscovery.com/category/key-scienti
„–®ÞÜÜÙÌêAKM®“®f=5/®VR6+®
[RZ: ÓáÇÅçGc½²‚ÞÄÈè×áÄêUPIII-Src
fic-articles/
Í ÏÔ à ¾ \  , . w 84& P R d 1 . ï: 9 @ ï
2013.9.26-28
“®Tƒ®;7C2®Y9®„–: ÂÛæÆÓ
áÇÅç^z€½³µ¿ATP¾b3¼ATPÄáìÎêÉ.
w84&PRd1.ï:9@ï2013.9.26-28
> 4 n u ®( ] | ® œ Q ® „ – ®; 7 C 2 : ÓáÇ
Åç¾Gc˜t½³µ¿"y¼`¾eE. w84&P
Rd1.ï:9@ï2013.9.26-28
„ – : z € ‚ Þ Ä È è × á Ä ê ½ 8 ' ¸ ¿ uroplakin III
(UPIII)-SrcÍÏÔà¾Xx¼hg\. PRÓáÇÅçov¡
ï|q@ï2013.9.23-25
A)+4/">*%68C7(&
,$1' @!?B: ÂÛæÆÓáÇÅç^z€½³
µ¿ ATP ¾b 3 ¼ATPÄáìÎêÉ. P R ÓáÇÅço v
¡ï|q@ï2013.9.23-25
Sato, K.: A possible membrane maturation mechanism in oocytes
of the frog Xenopus laevis. Ëì×êov‘°"y¼kh¾
15 2013 `F±ïÝæÞÏíÂáæÆîï2013.7.14-19
Ijiri, T.W., Kishikawa, J., Imamura, H., Sakiie, M., Ueno, S.,
Iwao, Y., Yokoyama, K., Sato, K.: ATP quantification and ATP
imaging in Xenopus laevis oocyte. Ëì×êov‘°"y¼
kh¾`F±ïÝæÞÏíÂáæÆîï2013.7.14-19
Sato, K.: A possible membrane maturation mechanism in oocytes
of the frog Xenopus laevis. EMBOéìÈÍäÒÝïÚØãçÏ
íÛåêÏîï2013.6.11-15
Ijiri, T.W., Kishikawa, J., Imamura, H., Sakiie, M., Ueno, S.,
Iwao, Y., Yokoyama, K., Sato, K.: ATP quantification and ATP
imaging in Xenopus laevis oocyte. FIR, DE, 2013.6.6-8
„ – : UPIII-Src signaling system in egg membrane
microdomains of the frog Xenopus laevis is required for
fertilization, can be reconstituted in HEK293-overexpression
system, and becomes functional after oocyte maturation. O1
†¢)ovÂ荋¢)‘ïV_@ï2013.6.1-3
14 2013 11 ~
! ! Prof. Nobuo Shimamotoƀ
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Assist. Prof. Hideki Nakayama.
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Research projects and annual reports
Among the enzymes, RNA polymerase is one of the
Nanobiology is a biology in which physiological changes
earliest to which new physical and chemical techniques
are described in terms of the movemants of biological
have been applied in mechanistic study. However, the
molecules. We push nanobiology in the fields of
following four problems are left contradictory. (1)
transcription and survival strategy of bacteria.
Dillemma on the binding to a promoter sequence: It must
1) B-maggio: a new GFP resistant to photobleaching
be strong enough to make a DNA bubble, while it must
We have invented a new GFP which may replace
be weak enough to allow the promoter clearance in
conventional GFPs now used for most purposes. It emits
elongation. (2) What is the significance of abortive
a green fluorescent with a peak at 512 nm with the
transcription, which seems to waste a lot of energy. (3) Is
excitation maximum at 493 nm as strong as GFPUV4,
sigma-70 released during transcription initiation. (4) The
which is supposed to be the brightest in E. coli.
contribution of the sliding along DNA in promotor
Therefore, abundant proteins can be easily visualized by
search. I have cited about 200 papers to examine the
fusing gfp with their genes in chromosome. Its most
contradictions. I found some contradictions are due to
distinct merit is the resistance against photobleaching,
ignorance of the technical limit of FRET, and the others
which is 250-fold and 110-fold stronger than Venus in
are due to the confusion between abortive initiation and
vitro and in vivo, respectively. This simplifies the focus
productive initiation with excluded NTP substrates.
adjustment in imaging, and a big inprovement in the
Reconsideration of published results enabled me to
tracing single fusion molecules.
propose a more consistent model for abortive initiation
2) Survival strategy of E. coli cells
where abortive transcripts are released by backtracking.
Bacteria can survive in non-growing conditions. In
In this model, RNA polymerase can stock enough energy
evolutional selection, this survival is as important as
as the form of DNA squrunching to clear the promoter
their growth, but the underlying mechanism is poorly
and release sigma-70 during early transcription in
understood because of the complexity of the problem.
productive conformation. The polymerase can
Since cell must degrade their used proteins to salvage
alternatively form another conformation with less
amino acids for their survival, we at first focused on the
contacts with signa-70, which allow itself to backtrack to
relationship between this protein turnover and tmRNA.
release abortive transcript but inhibits sigma-70release
The tmRNA (ssrA) and SmpB induce the degradation of
and promoter clearance. This model provides the
nascent polypeptide by ssrA-tagging in response to a
answers of the problems (1)~(3). In addition, I pointed
reduced level of amino acids in stationary phase. We
out the confusion of Brownian motion and the
prepared the disruptants of genes relating to the tmRNA
transition-state theory. Therefore, the two-pawl ratchet
system as well as major chaperons and AAA+proteases.
mechanism of elongation is still possible to be
Unexpectedly and probably fortunately, most examined
non-Brownian. This misunderstanding led several wrong
protease/chaperon genes are synthetic lethal with ∆ssrA
conclusion on the existence of sliding even in the recent
or ∆smpB, demonstrating that there are two parallel
papers (Chem Rev). This more strict understanding of
pathways in the surviving mechanism. One is dependent
chemicsl reaction enabled the reconsideration of a
on the tmRNA system, and the other on clpA, clpP, clpX,
pausing phonomenon (Transcription, 2013).
dnaJ, hslU, hslV, htpG, prc, and sspB, at least. Among
ƀ
the examined genes, non-synthetic-lethal genes were
74310!
only clpB and lon, which could be thus involved the
ƢƮƯƲƧƲƴƹƴƀƞƆƀƞƧƳƴƨƯƴƱƴƭƼƀƴƬƀơƞƒƀƵƴƱƼƲƫƷƧƸƫƑƀƓƯƴƱƴƭƯƩƧƱƀ
tmRNA pathway. Another conclusion is that the
ƔƴƳƸƫƶƺƫƳƩƫƀƴƬƀƚƳƮƴƲƴƭƫƳƫƯƹƼƀƯƳƀơƫƧƩƹƧƳƹƄƀƔ
Ɣ Ʈ ƫ Ʋ Ɔ ƀơ ƫ ƻ Ɔ ƀ
tmRNA-dependent degradation is not contributing to the
protein turnover, because the main proteases in the
Ɖ Ɖ Ƌ Ƅ ƀ ƐƌƈƈƅƊƊƀ
system, ClpXP, ClpAP, and Prc(Tsp), are synthetic
lethal.
ƚƲƧƸƮƯƲƯƽƺƀƝƄƀƢƮƯƲƧƲƴƹƴƀƞƄƀƟƸƮƯƲƧƀƣƄƀƜƧƸƮƱƫƻƄƀƝƆƀ
3) Nanobiology of RNA polymerase
ƣƷƧƳƸƩƷƯƵƹƯƴƳƀƫƱƴƳƭƧƹƯƴƳƑƀƙƫƹƫƷƴƭƫƳƴƺƸƀƹƷƧƩưƯƳƭƀƴƬƀơƞƒƀ
ƵƴƱƼƲƫƷƧƸƫƀƧƳƪƀƨƯƴƱƴƭƯƩƧƱƀƚƲƵƱƯƩƧƹƯƴƳƸƆƀƣ
ƣƷƧƳƸƩƷƯƵƹƯƴƳƀ
ȆǼȨȗȄȮȫȭȀȉȔǸǀoąJǀq®ů: ȗȂȏȧǸ 1
ēĠǦǣȌȬȘȂŋȓȖǺȬȇǼȂȆȥȬ. Č 7 K ēĩ_ħ
ƍƄƀ
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oąJǀq®ů: +AAA proteases Ǟ tmRNA
ƔƴƺƷƸƫƄƀƋƷƪƀƫƪƆƀƓƴƱƸƴƻƫƷƄƀƢƆơƆƄƀƢƮƫƵƮƧƷƪƄƀƖƆƒƆƄƀƦƮƯƹƫƄƀ
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2013. 8. 7-9
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ȆǼȨȗȄȮȫȭȀȉȔǸǀoąJǀq®ů: ȴȳȳȼȦǺȞȋ
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oąJǀž¿ſû]ǀq®ůƀ áķ%Źƀ ¢ĵīȌȬ
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Japan-India Joint Symposium on Protein-DNA Interactions in
Prokaryotic Nucleoid and Eukariotic Chromatin, Singapore
ȶȰƀ _VÎ.ƀ ƀ
National University, Singapore, 2013. 7. 22-23
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RhoA <Ñ­}"%:RhoA 1Ñ­}/&®­=ø
ŕŮŅlņţńĶĩīĪĚĦ ōܲÆÒřŐŝţŠŏń
ā1Ë.۔<qĔ$:15)º8-2/
¯ÆÒŢD‘Ş¡LűûŕŮőŞńŗœŜńŗŢû
RhoA 1Ñ­}<ġ™$:!.·(/±=ÏãzĬx
*ƒţܲÆÒŞ¯ÆÒš°ŸŕŮƇƓƚƗƋƕƘ
“Éæąĭ1ğå0¿|-:.Ā8;:
ĚĝƛıijIJĝƜűŕŮŻŹƆƖÿšLŕŮőŞű¹œŘŅ
÷ ½ f Ɗ Ƅ ² Ö m U ² ¯ ¥  Ţ ĨĮİĚĝ Æ Ò ţ ń
LHF E=mztlnx0/4-3$ M {
ĶĩīĪĚĦ ű°Ÿœ ĶĩīĪĚĦ ţ ıijIJĝ űœŜ ĨĮİĚĝ Æ
|‚†}ˆ PFGRSRXMTTT\Humz<‰~„ˆ
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ƚ\kţ<bœŠŌŚŘŅőůŬŢɃŌŬńıijIJĝ ŢÆ
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ŹƆƖűÿŕŮŘŨšcďŝŇŮőŞō|ŬŌšŒů
œŘŅŗŢɃńĒþōŲÆÒš ĪīĪijğĭĭĭķ Ţ°Ÿōé
ŘŅŒŬšńıijIJĝ ŢÆÒĐ@ţõCƀƘƉŸóŝŇŮ
ŨŬůŘōńčtŕِT²ÆÒšţ ĪīĪijğĭĭĭķ Ţ
īĭIJħĝ ŞńijĺľīĩĪ ŝŇŮ ĴŃł ŞÉ4œńīĭIJħĝěĴŃł à4
°ŸţéŨŬůŠŌŚŘŅŧŘńĪīĪijğĭĭĭķ Ţ°Ÿōé
\kűêRŕŮőŞű¹œŘŅ'ŊŜńīĭIJħĝěĴŃł à
ŨŬůŘōŲÆÒšŋňŜÆÒD‘ƎƚŵƚŝŇŮ
4ţÆÒĔˆŢÌkšċŰŮ
įĻĢģ ō…ØŒůŘőŞŌŬńĪīĪijğĭĭĭķ Ţ°ŸōōŲÆ
KĄ ī ƀƘƉŸ
óŝŇŮ ijĺľĦ ű—f,ŕŮőŞű|ŬŌšœŘŅŧŘń
ÒŢD‘űûœŜňŮőŞō¹:ŒůŘŅ¸¾ŝţń
ĒþōŲšŋŐŮ ĪīĪijğĭĭĭķ ŢōŲif,ûƐŵƇž
Ė Ė Ė In
Əűä‚ŕŮŘŨšńĪīĪijğĭĭĭķ Ţ°ŸōňĒþōŲ
anti-angiogenic drug for the treatment of metastatic
ÆÒ‡Ţ ĩħīĭĚĝĜ ű£ňŜ‰åœŘŅĩħīĭĚĝĜ ÆÒš
colon cancer, bevacizumab (Avastin, Genentech) based
ĪīĪijğĭĭĭķ űý%°ŸŒŖŮőŞšūŭńÆÒD‘ÓŢ
on Judah Folkman’s hypothesis that tumor growth is
ûōéŨŬůŘŅĪīĪijğĭĭĭķ ŢƂƗŻƘƕƘă,ōéŨŬ
angiogenesis-dependent and that its inhibition might be
ůŘőŞŌŬńĪīĪijğĭĭĭķ ō—f,ŒůńĒþōŲÆÒŢ
therapeutic.
D‘ŻŹƆƖō—f,œŜňŮőŞō¹:ŒůŘŅŒŬšń
antibody that neutralizes the vascular endothelial growth
ĪīĪijğĭĭĭķ °Ÿ ĩħīĭĚĝĜ ÆÒŝţńĪīĪĝĤ "›šūŭ
factor (VEGF-A). Malignant tumors express VEGF-A
ŒŬšÆÒD‘ÓŢûōéŨŬůŘŅĪīĪĝĤ Ţ°Ÿ
which recruits blood vessels, thereby supplying tumors
ţĒþōŲÇÍŢËÊÙÆÒŝĕŏŠŚŜňŮőŞō
with oxygen and nutrients that promote tumor cell
B8ŒůŜňŮőŞŌŬńËÊÙÆÒŌŬ
migration
•ŒůŘ
2004,
the
U.S.
Avastin
FDA
is
a
proliferation,
approved
humanized
survival,
the
first
monoclonal
and
metastasis.
ĪīĪĝĤ šĒþōŲÆÒŢ ĪīĪijğĭĭĭķ ō0dŕŮőŞšū
VEGF-A signals via a tyrosine kinase receptor, VEGFR2,
ŭńĒþōŲÆÒŢD‘ÓōûœŜňŮőŞō¹:Œ
are blocked by Avastin to suppress tumor angiogenesis.
ůŘŅ ŢɃŌŬńĒ þ ōŲšŋňŜńĪīĪijğĭĭĭķ
However the impact on overall survival is not well
°Ÿō{ŕŮőŞšūŭńĒþōŲŢif,ōûœ
documented and in fact some tumors are no longer being
ŜňŮőŞō¹:ŒůŘŅĖ
treated with Avastin. Neuropilin-1 (NRP1), a 130kDa
MHF ~ Œ ‡ Ž ) 2 ? ( & NdegcadIK v
transmembrane protein known as another VEGF-A
V^hfadIK twxBAyCoxkF
receptor expressed in some malignant cancer cells.
Ė ŵƖƎƘ¬Ïţń; \kŋūŤ;ÅĈާTŞ
Therefore, it has been thought that NRP1 may induce
„ffՎӬűʼnIfªhŝŇŮōńŗ
tumor proliferation, migration and survival, but its
Ţ
mechanisms remain to be fully elucidated.Ė
KA³šśňŜţŦŞŲş|ŬŌšŒůŜňŠňŅ
lņţńƀƘƉŸóƍƑƗżƚsÅšūŭŵƖƎƘ¬
In this study, we showed that NRP1 indeed acts as
Ï/=ĀK ŢĀK¢ŝŇŮ ĦĽľŀļĻĽĚĝ
VEGF-A
ō ; Å \ k ű ! a ŕ Ů ıĸŁĿĻĽĚĝ Ż Ź Ɔ Ɩ Ţ 2 P proliferation signaling into the cells. Actually, VEGF-A
ıĸľĹĸĽĻĽ ŋūŤ Ĩħħ Şĕňµ5fōŇŮőŞűâœń
binding to tumor expressing NRP1 activated RhoA
ĦĽľŀļĻĽĚĝ ōÆÒFŝ ıĸŁĿĻĽĚĝ ޵£œŜňŮőŞ
activity through the complex formation with GIPC1 and
ű¹œŘŅáÍģÐ<Ý(—ĩ8
Syx that are expressed in the cells with the NRP1
. è´æ0ú…$:!.<º80#
cytoplasmic domain, thereby inducing a proliferative and
( 5 ( 1 Û Ø • æ Ñ ­ 3  4 $
survival signal in the tumor cells.ĖDJM-1 cell, malignant
1§Ħ<ÆČ#(íùöøāÄ-:
skin cancer cell line, expresses VEGF-A and NRP1
<x}č›#íùđ÷tó1¯ĝvĜ<¦¯"
endogenously. The malignant cancer cells can proliferate
%(© Ù5(2 . well
<‡¼Ô{#('1ú Ù-2¯ĝ
VEGF-A or NRP1 expression by siRNA treatment in the
vĜøāćĥ0åÚ$: ƒšn0oÝ#¯
cells inhibited the cancer cell proliferation in 3D agar
ĝvĜ< ‘"%( < .‡
culture condition. However, Avastin did not inhibited
¼0Ô{$:.¯ĝvĜ1 ‘Ċ8;/*(
colony formation, suggesting that NRP1 mediates
!1úÂ8 2 1¯ĝvĜ VEGF-A
‘1øāuFELYlĖ<ġ™#,:!.º8
cytoplasmic deletion mutants in DJM-1 cells where
0/*(j^1úÂ<5.6. endogenous NRP1 expression was abrogated with NRP1
in
receptor
in
tumor
cells
anchorage-independent
signals.
Lentiviral
to
manner.
expression
transduce
Silencing
of
NRP1
.è´æ0ú…$:!.079
shRNA did not restore the colony formation, while
FELY<ġ™#,:!.ì‹";(½/:
lentiviral
x“UCMHT<ċº$:a–-:Ė
Co-immunoprecipitation experiments showed that two
proteins, GIPC1 and Syx interacted with the NRP1
3. Research projects and annual reports
cytoplasmic region. Knock down of either GIPC1 or Syx
1)FF VEGF-A induces VEGFR-independent signaling,
expression in DJM-1 cells, as well as VEGF-A or NRP1
Neuropilin dependent Tumorigenesis.Ė Ė
siRNA treatment of the cells, inhibited tumor colony
expression
of
wild
type
NRP1
did.
NRP1
that expression of FGF18 was upregulated in fibroblast
cytoplasmic region requires interaction with GIPC1 and
of esophageal cancer. Therefore, cell proliferation of
Syx to induce tumor proliferative and survival signals.
esophageal carcinoma may be enhanced by FGFR3IIIc
Pull-down assay of active RhoA showed that siVEGF-A,
binding to FGF18 from fibroblast in esophageal
NRP1, GIPC1 or Syx treatment inactivated RhoA
carcinoma. These results indicate that the upregulated
activity. These results indicate that the NRP1 signal
expression of FGFR3 IIIc in human ESCC enhancesF cell
activates RhoA to promote DJM-1 cell proliferation.Ė
proliferation and may promote tumor progression.Ė
2: Enhanced Expression of Fibroblast Growth Factor
3: Anosmin-1 inhibits Netrin-1-induced growth cone
Receptor 3 IIIc Promotes Human Esophageal Cancer
collapse. Ė
formation.
These
results
suggest
that
the
Malignant Progression.Ė
Kallmann
syndrome
is
characterized
by
Ė Ė Ė The expression of FGFR isoforms is temporally and
hypogonadism due to gonadotropin-releasing hormone
spatially regulated in embryos and in normal adult
(GnRH) deficiency, and a defective sense of smell
organs. Alternative splicing of the FGFR gene has been
related to the defective development of the olfactory
implicated in carcinogenesis. Switch expression of
bulbs and olfactory tracts. This syndrome is caused by
FGFR to mesenchymal isoforms, enabling cells to
mutations affecting the KAL1 gene, which codes for the
receive signals usually restricted to the connective tissue.
extracellular protein anosmin-1. However, the molecular
FGFR3 has two different transmembrane-type isoforms,
pathogenesis is poorly understood. In the previous study,
FGFR3 IIIb and IIIc, which are produced by alternative
we show that Anosmin-1 FNIII repeats also show 40% of
splicing and have distinctive ligand-specificities. In
homology with Netrin-1 receptors DCC and Neogenin,
normal tissues, IIIb isoform is mainly expressed in the
which are expressed by growing nerve cells in the
epithelium, whereas IIIc isoform is mainly expressed in
developing vertebrate brain. In addition, the Netrin-1
the mesenchyme. In the previous study, we found the
Knock-out mouse shows defective of the olfactory tracts
expression of FGFR3IIIc isoform was upregulated in the
and the migration of GnRH neuron. We hypothesized
86% of the human esophageal squamous cell carcinoma
that Anosmin-1 acts as a soluble receptor for Netrin-1,
(ESCC) specimens analyzed by RT-PCR. However, it
thus Anosmin-1 inhibits axon guidance cue of Netrin-1.
was unclear whether the enhanced expression of FGFR3
F F F In this study, the role of Anosmin-1 as an inhibitor
IIIc is due to cancer cells or to increased mesenchymal
for Netrin-1-induced growth cone collapse was tested.
cell population to the tumor region by inflammatory
First, we tested whether Anosmin-1 and Netrin-1 bind
infiltration.
ĖĖ
directly by immunoprecipitation assay using condition
Ė Ė Ė To clarify this, we performed immunostaining of
medium
tumor sections obtained from esophageal cancer patients
expressing HEK293T cells. The result showed that
and showed that FGFR3IIIc was specifically expressed
Anosmin-1directly bound to Netrin-1. Next, to determine
in the human ESCC but not the adjacent normal
Anosmin-1 regulate biological activity of Netrin-1, we
epithelial cellsuggesting that it is upregulated during
performed the growth cone collapse assay. As a result,
tumor
of
Netrin-1 alone induced growth cone collapse. In contrast,
FGFR3IIIc in ESCC was consistent with expression of
co-treatment of growth cones with Netrin-1 and
Ki67 by immunostaining, suggesting that the expression
Anosmin-1 did not induce the collapse. These results
of FGFR3IIIc in ESCC enhances cell proliferation.Ė
suggest that normal Anosmin-1 may act as an inhibitor
Ė Ė Ė In order to further demonstrate the effects of FGFR3
for the signal of Netrin-1-mediated growth cone collapse
IIIc expression, we analyzed cell proliferation of FGFR3
in the developmental process of the central nervous
IIIc-overexpressing human ESCC, ECGI-10. The effects
system, contributing to an elongation pathway of the
of FGFR3IIIc overexpression increased cell proliferation
olfactory axons and the associated migration of GnRH
by autophosphorylation of FGFR3IIIc in no addition of
neuron.
progression.
Moreover,
the
expression
FGFs. Moreover, reactivity of FGFR3IIIc to FGF18 in
was
F
upregulated by cell proliferation assay. It was reported
F
FGFR3IIIc-overexpressed
ECGI-10
cells
of
Anosmin-1-Myc-
and
Netrin-1-V5-F
”‘:5srF
–‘pu'9DF
M. Fukami, M.Iso, N. Sato, M. Igarashi, M. Seo, I. Kazukawa,
ƝƜĖ Fāñą
E. Kinoshita, S. Dateki, T. Ogata: Submicroscopic deletion
¼M¸¾ðß(ąƙA³ƛħƜĖ
involving the fibroblast growth factor receptor 1 gene in a
ë đ 6 Ƥ¦ K I f „ f f Õ Ž Ó ¬ h Ñ Ţy œň
patient
çx–Ţĉ°Ş”®ŶŴƅƔŴƘŢkĖ
with
combined
pituitary
hormone
deficiency.
¸¾
Endocrine J. 60(8):1013-1020 (2013.5)
A. Shimizu, H. Nakayama, P. Wang, C. Konig, T. Akino, J.
pÑƤœSÎĆęĖ 1`VXƤĬĞĠĚĞĢ VĖ ėğ VĘĖ
5¸¾ƙŴƘƀƚƌƗƃŴƘ‡YºĖ
Sandlund, S. Coma, JE. Jr. Italiano, A. Mammoto, DR.
ëđ6ƤVEGF ŻŽƃƏìÃÛŢŽŸƕƚƇƘŹÄšċŕٸ
Bielenberg, M. Klagsbrun:Netrin-1 promotes glioblastoma
¾Ė ¸¾
pÑƤœSÎĆęĖ 1`VXƤĬĝĥĚĞġ VĖ ėģ VĘĖ
cell invasiveness and angiogenesis by multiple pathways
ƞƜĖ ·ïÀĖ ŠœĖ
including
ƟƜĖ MF—+Ė œSÎĆƤz¡,Mèî9Ė
activation
of
RhoA,
cathepsin
B,
and
cAMP-response element-binding protein. J. Biol. Chem.
Ė Ė Ė Ė Ė Ė Ė Ė Ė ¹ÀÛ}•kĒà¶ĘiďŠ (2010.10.1)
288(4): 2210-2222 (2013)
¹ÀÛ}•kĒà¶Ę£b (2011. 10.1 )
C. Waga, H. Asano, T. Sanagi, E. Suzuki, Y. Nakamura, A.
Ė Ė Ė Ė Ė Ė Ė Ė Ė œSÎĆƤĂW°|À&)ÑÞ]Q†J9Ė
Tsuchiya, M. Itoh, Y. Goto, S. Kohsaka, S. Uchino,
ƠƜĖ 2òÀĖ ŠœĖ
Identification of two novel Shank3 transcripts in the
ơƜĖ ŗŢ
Ė Ė
1) œSÎĆƤĂW°|À&)ÑÞ]Q†J9ŞœŜń¿
developing mouse neocortex. J. Neurochem. 128(2): 280-93
ơƢ<ĂW°|À&)ÑŢQ†űÝŚŘŅ2013 V 3 }
(2014)
2) œSÎĆƤ•k¤ĝ øāË\xĈ\=
•‘*6sr
¿ ĢĜ < Ė z  ¡ , M ù ¨ w ā ńH Č H M 7 ¤ ŷ
ƒƘƉŽĖ - M ā ƙć € ē ń2013.5.18
M. Seo, A. Yoshida, A. Shimizu, VEGF-A/NRP1 signaling
induces GIPC1/Syx complexes, resulting in RhoA activation
לýěĮeęÜǒ•Ģīôû³Ç øā
to promote survival and growth of human malignant skin
.wÛ~ã31¬Ý<—¸#(
cancer cells. Vascular Biology Program, Prof. Klagsbrun’s
לýě.לëñ˜ĮŸžéòŸžµž`•ÃÛª
invitation, Children’s Hospital Boston, Harvard Medical
1eęër1(61Ďÿ¹À1¾tó~ã
x“Éæ
School, Boston, U.S. A. 2013.4.11 ėq_íšĘ
ą0+,h<—¸#(
† Þ c m ý Õ Ì » ß Michael Klagsbrun × œ ý ě Į
VEGF-A/NRP1 FELY2OK®­çăäøā1Ë
Ė
<qĔ$:õ 60 ¹ÀÛ}•kĒà¶ĘpkˆÞ¡
Ė
2013.5.18Ĭ„ħåćRGI]åćĭ
Ė
Ė
ôuîfÕ̻ߟÀÎêĨלýěĮAnosmin-1 0
7: RGMa 1¯ĝvĜ ‘oÝ1ġ™ÊÈ1ċºõ 60
Ė
¹ÀÛ}•kĒà¶ĘpkˆÞ¡2013.5.18. Ĭ„
Ė
ħåćRGI]åćĭ
Ė
†ÞcmýÕÌ»ßMichael Klagsbrunלýě Į
Ė
VEGF-A/NRP1FELY2OK®­^ç=øā1Ë
Ė
<B]KDX[07*,qĔ$:õ17¹À=x“É
Ė
æÏã•k•ĆĤkeę¡2013.6.12-14ĬZ]DFV
Ė
JQĭ
Ė
ÓĚ¥ŒĮS@G’ĂçĐåĖĕð0
:ĄĞâĠēx“
Shank31NX>[KåÚċÁN?BPA]WT2013e
ęÜǒ•ü…Û‰ï•Ę2013.7.19Ĭ²¨ĎÖĭ
ôuîfÓĚ¥ŒÕÌ»ßלýěĮCYS[âsþ
€Žėl“ÜØAnosmin-12đ÷‚厓RGMa.Netrin-1
1¯ĝvĜ1 ‘oÝ<ġ™$:õ36¹Àx“Ûؕ
k¢kí°¡2013.12.5ĬRGI]åćĭ
¸ ¾ O ¶ Ƥĝġ 3 ē á šŜń. Š æ e ųƖƈƏ£ šv ^
ƛĞĜĝğ Vƣ}ƞƢzƜĖ
9 #9 Prof. Hiroshi Nakada, Ph.D.ĵ
BGHPQGRPQT9PJ9ANNSOPKMTIPHLPMPKT9
9 *#9 29
Assist. Prof. Kaoru Akita, Ph.D.
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İƚĆŰą„,ƅŮƕŬU‘Ɗ ŒĸƧNJƣǎƚ‹ƂĴ,
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ŰŪĸƣƴƸǎƆ ŐŗŇļĸŇň Ɗ&¶ƉƂůƄ¨ĉŻƀŭſ
Research projects and annual reports
Ɗë ¢ŬŪĸƣƴƸǎƋŬƪƧnjƳƦ ń ƊÁ u Y Ó Ɖ
Mucins are major components covering the luminal
ŐŗŇļĸŇň ƉNJƦNjǐƵź Ɨƀŭſ Ɗx Ŭ ŪĸƣƴƸǎ Ɔ
surfaces of the epithelial respiratory, gastrointestinal,
and reproductive tracts, and are high molecular weight
MUC1 C-terminal domain. The recruited -catenin was
glycoproteins with a number of O-glycans.
thereafter transported to the nucleus, leading to cell
We have been studying on the function of these mucins
growth. These findings suggest that Siglec-9 expressed
with respect to tumor progression. It is well-known that
on immune cells may play a role as a potential
most of tumor cells are derived from the epithelial cells.
counterreceptor for MUC1 and that this signaling may be
Since normal epithelial cells exhibit a clear polarity,
another MUC1-mediated pathway and function in
synthesized mucins are transported to be the apical cell
parallel with a growth factor-dependent pathway.
surface and become secretory or membrane-bound
In addition, soluble lectins may be present in tumor
glycoproteins. Upon malignant transformation, mucins
microenvironment. We performed a similar experiment
are transported to whole cell surface, and then some
using MUC1-expressing 3T3 cells and recombinant
mucins
and/or
galectin-3. It is revealed that galectin-3 binds to
bloodstream of cancer patients because of loss of the cell
MUC1-N-terminal domain and thereby initiates similar
polarity of epithelial tissues.
MUC1-mediaited signaling.
are
secreted
into
tumor
tissues
In tumor microenvironments, soluble lectins and
mucins may be ligands for membrane-bound mucins and
2: Negative regulation of TLR-4 mediated signaling
lectins, respectively. Membrane bound mucins may be
through
counter receptors for membrane-bound lectins. Binding
monocyte-derived immature dendritic cells (imDCs)
of lectins to membrane bound mucins expressed on
were
tumor cells is expected to start signaling and play a role
anti-Siglec-3/CD33 mAb, the production of IL-12 and
in tumor progression. In addition, binding of mucins to
phosphorylation of NF-B decreased significantly. The
siglec family expressed on immune cells may lead to
cell
down-modulation of immune cells because many siglecs
cross-linked, and Siglec-3-linked proteins were analyzed
possess
by SDS-PAGE and immunoblotting. It was CD14 that
immune-regulatory
motif.
These
mutual
ligation
stimulated
of
CD14
with
LPS
with
in
Siglec-3. When
the
surface proteins of imDCs
presence
were
of
chemically
was found to be cross-linked with Siglec-3. Sialic
interactions may facilitate the tumor progression.
acid-dependent binding of Siglec-3 to CD14 was
1: Biological function of membrane-bound mucin,
confirmed by plate assay using recombinant Siglec-3 and
MUC1, produced by epithelial cancer cells. Because
CD14. Three types of cells: HEK293T cells expressing
MUC1 carries a variety of sialoglycans that are possibly
the LPS receptor complex (TLR cells), and the LPS
recognized by the siglec family, we found that Siglec-9
receptor
prominently bound to MUC1. An immunochemical study
(TLR/SigWT cells) or mutated Siglec-3 without sialic
showed
acid-binding activity (TLR/SigRA cells) were prepared,
that Siglec-9-positive immune
cells
were
fibroblast cells and a human colon cancer cell line,
revealed that wild-type Siglec-3 but not mutated Siglec-3
HCT116, stably transfected with MUC1cDNA were
significantly reduced the phosphorylation of NF-B, due
ligated with recombinant soluble Siglec-9, -catenin was
to inhibitory effect on the presentation of LPS from
recruited to the MUC1 C-terminal domain, which was
CD14 to TLR4 through ligation of CD14 with Siglec-3.
enhanced on stimulation with soluble Siglec-9 in dose-
ĵ
and time-dependent manners. A co-culture model of
kh6g1YX9
MUC1-expressing cells and Siglec-9-expressing cells
H. Yurugi, S. Tanida, K. Akita, A. Ishida, M. Toda, H. Nakada.
mimicking the interaction between MUC1-expressing
Prohibitins function as endogenous ligands for Siglec-9 and
malignant cells, and Siglec-9-expressing immune cells in
negatively regulate TCR signaling upon ligation. Biochem.
a
Biophys. Res. Commun. 434(2): 376-381 (2013)
Brief
uptake
of
Siglec-3
phosphorylation of NF-B were investigated. It is
designed.
and
wild-type
and
was
binding
either
pancreas, and breast tumor tissues. When mouse 3T3
microenvironment
the
plus
associated with MUC1-positive cells in human colon,
tumor
then
complex
LPS
and
co-incubation of Siglec-9-expressing HEK293 cells, but
Y. Matsumoto, Q. Zhang, K. Akita, H. Nakada, K. Hamamura,
not mock HEK293 cells, with MUC1-expressing cells
A. Tsuchida, T. Okajima, K. Furukawa, T. Urano. Trimeric
similarly enhanced the recruitment of -catenin to the
Tn antigen on syndecan 1 produced by ppGalNAc-T13
enhances cancer metastasis via a complex formation with
§ ĵ 2 ŬÞ Ì ĵ ü Ŭ% ³ C Ŭ¿ Ì Ĩ Ŭ p f v ñ Ŭ Ìĵ
integrin alpha5beta1 and matrix metalloproteinase 9. J. Biol.
7ǚŐŗŇļ ÒÅèôƉŲŷƖ ŧœŅ ƊĎ_ǔã łĽ G–ŸÑZ
Chem. 288(33): 24264-24276 (2013)
ZĀîŬ®ºjŬĽĻļľĹļĻĹľĸŀĵ
S. Tanida, K. Akita, A. Ishida, Y. Mori, M. Toda, M. Inoue, M.
ĵ
Ohta, M. Yashiro, T. Sawada, K. Hirakawa, H. Nakada.
mhV[589
Binding of the sialic acid binding lectin, Siglec-9, to the
ǕǒTģėħ
membrane mucin, MUC1, induces recruitment of beta-catenin
ßZÛâĖĂ1ħǏLÕÛâǑŇǒĵ
and subsequent cell growth. J. Biol. Chem. 288(44):
ďı?ǚīåNJƠǂƲƉŲŷƖƬƿƞǎƨƪǎ ļ NJǎĥnjƭǀư
31842-31852 (2013)
ǐľǑŕōœľǒƊ
Ûâ,ŠðǚÌĵ 7Ŭĵ :zquǚŌĽľĸĽŀ qǑľ qǒĵ
N. Zamri, N. Masuda, F. Oura, K. Kabayama, Y. Yajima, H.
Nakada,
K.
Yamamoto,
Y.
Fujita-Yamaguchi.
Characterization of anti-Tn-antigen MLS128 binding proteins
ŵĵ
ĵ
ZĀÛâ1„Lħ1„ħǏû†ÛâǑņǒĵ
involved in inhibiting the growth of human colorectal cancer
ďı?ǚæĩIJƊiÏƉLƃůƀ•YƊ8gÑþ½Ċ’
cells. Biosci. Trends. 7(5): 221-229 (2013)
ǂǐƣǐƊøtÓ(ċĵ
ÛâāðǚÞÌĵ üŬĵ :zquǚŌĽŀĸĽŁ qǑĽ qǒĵ
K. Akita, M. Tanaka, S. Tanida, Y. Mori, M. Toda, H. Nakada.
CA125/MUC16 interacts with Src family kinases, and
ĵ
over-expression of its C-terminal fragment in human
ǖǒÙĕ­äĵ ƈŻĵ
epithelial cancer cells reduces cell-cell adhesion. Eur. J. Cell
ĵ
Biol. 92(8-9): 257-263 (2013)
ǗǒZT¸3ĵ
S. Tanida, Y. Mori, A. Ishida, K. Akita, H. Nakada. Galectin-3
Ìĵ 7ǚĵ }dVZįn4đmĵ
binds to MUC1-N-terminal domain and triggers recruitment
Ìĵ 7ǚĵ ĤƺƟƢƿơǐljDŽr
ĵ
of beta-catenin in MUC1-expressing mouse 3T3 cells.
Ìĵ 7ǚĵ ßZ‡Āù±«…ÎÓƟƹǁǐƪLjǎĠģƝ
ƶƺƟƩǐĵ
Biochim. Biophys. Acta. in press.
ĵ
Ìĵ 7ǚĵ őʼnňŒ ƾƝnjƽLJǐƝǐĵ
lh%3YXĵ
Ìĵ 7ǚĵ –ŸÉ5ZċĒDĵ
Y. Yurugi, H. Nakada. Interaction between Siglec-9 and
Ìĵ 7ǚĵ –ŸæęZċĒDĵ
prohibitins down-regulates T cell receptor signaling. The 15 th
ĵ
International Congress
ǘǒ;Ęäĵ ƈŻĵ
of
Immunology,
Milan
(Italy),
ĵ
2013.8.22-27
Ìĵ 7ǚŐŗŇļ ÒÅèôƉŲŷƖƠǍƥƷǐƮƊÒÅĎ_ǔ
ã ĽĽ G – Ÿ Ŵ ƛ ě à Z Z Ā Į Ǐ î Ŭ ¡ Ÿ j Ŭ
ǙǒſƊĵ
 ĵ òǚ ĵ Ĥ Ê ©V Z VZ ĭǏ xœ 7 Rď á ŬZ ǑhZ7Rǒ:z
ĽĻļľĹłĹļļĸļĽ
Ìĵ 7Ŭĵ òŬēÌApŬỨlXŬÞÌĵ üǚƪƧnj
ƳƦĸń ƉƓƖǀǍƼƽƲǎƚŻƀ ŖŇŔ ƪƧƷNjĢƊˆ/ǔ
Ûâ\DžǎƺǐƊ)×ĵ
ã ľĽ G–ŸæęZqŬVĬjŬĽĻļľĹŃĹŀĸłĵ
ĵ
ĵ
§ĵ 2ŬÞÌĵ üŬÌĵ 7ǚŐŗŇļ ÒÅƉƓƖ ŧœŅ ƊÒÅ
Ď_ǔã ŃŁ G–ŸÉ5ZVŬ®ºjŬĽĻļľĹńĹļļĸļľĵ
Ú Ì› l XŬÞ Ì ĵ ü Ŭ Ìĵ 7ǚŇňļĿĵ Ɔĵ ŕŝŜşśŚĸľĵ Ɗë =
ƉƓƖĵ ŖŢşşĸşŝŞśĵ ŤśŚśţŦŢŤĸĿĵ ƪƧƷNjĢƊˆ/ǔã ŃŁ G
–ŸÉ5ZVŬ®ºjŬĽĻļľĹńĹļļĸļľĵ
N. Zamri, F. Oura, N. Masuda, Y. Yajima, H. Nakada, K.
Yamamoto,
Y.
Fujita-Yamaguchi:
Characterization
of
anti-Tn-antigen MLS128 binding proteins involved in growth
inhibitory effects on human colon cancer cells. ã ŃŁ G–Ÿ
É5ZVŬ®ºjŬĽĻļľĹńĹļļĸļľĵ
ศᏊ⣽⬊⏕≀Ꮫ◊✲ᐊ ᩍᤵ㻌 Ọ⏣㻌 ࿴ᏹ
Laboratory of Molecular and Cellular BiologyProf. Kazuhiro Nagata, Ph.D
ຓᩍ㻌 ₻⏣㻌 ு㻌
Assist. Prof. Ryo Ushioda, Ph.D
䠍䠊◊✲ᴫせ㻌
䠏䠅㻌 䝍䞁䝟䜽㉁ရ㉁⟶⌮䛻䛚䛡䜛ᑠ⬊య䝺䝗䝑䜽䝇䝛䝑䝖㻌
㻌 㻌 ศᏊ⣽⬊⏕≀Ꮫ◊✲ᐊ䛷䛿䚸䛂䝍䞁䝟䜽㉁䛾୍⏕䛃䜢኱䛝
䝽䞊䜽䛾ព⩏㻌
䛺◊✲䛾ᯟ䛸䛧䛶タᐃ䛧䚸䝍䞁䝟䜽㉁䛾ㄌ⏕䛛䜙Ṛ䜎䛷䛾䝯䜹
ᑠ⬊య䛻䛚䛡䜛䝆䝇䝹䝣䜱䝗⤖ྜ䛾ᙧᡂ䚸ゎ㞳䛿䚸䝍䞁䝟
䝙䝈䝮䜢୰ᚰ䛻䚸୰䛷䜒䚸≉䛻䛂ศᏊ䝅䝱䝨䝻䞁䛻䜘䜛䝣䜷䞊
䜽㉁ရ㉁⟶⌮䛻䛚䛔䛶䛝䜟䜑䛶㔜せ䛺཯ᛂ䛷䛒䜛䚹ᑠ⬊య
䝹䝕䜱䞁䜾䛸⣽⬊ᶵ⬟ไᚚ䛃䛚䜘䜃䛂䝍䞁䝟䜽㉁ရ㉁⟶⌮ᶵ
䛻䛚䛡䜛㓟໬㑏ඖ䛻㛵䜟䜛ศᏊ⩌䛾⥙⨶ⓗゎᯒ䛸䛸䜒䛻䚸䝃
ᵓ䛃䛻↔Ⅼ䜢䛒䛶䛶◊✲䜢㐍䜑䛶䛔䜛䚹௒ᖺᗘ䜒ᘬ䛝⥆䛝䚸䛣
䜲䝖䝌䝹䛛䜙ᑠ⬊యෆ⭍䜈䛾䝅䜾䝘䝹ఏ㐩䜢௓䛧䛯䛭䜜䛮䜜
䛾◊✲┠ᶆ䛻ἢ䛳䛯◊✲䜢᥎㐍䛧䛯䚹ᚑ᮶䛾◊✲┠ᶆ䛻ຍ
䛾ᜏᖖᛶ䛾䜽䝻䝇䝖䞊䜽䛻䛴䛔䛶ゎᯒ䛩䜛䚹㻌
㻌
䛘 䛶 䚸 ᮏ ◊✲ ᐊ䛷 䜽 䝻䞊 䝙 䞁䜾 䛧 䚸 ࿨ ྡ 䛧 䛯 ᪂つ 㑇 ఏ Ꮚ
㼙㼥㼟㼠㼑㼞㼕㼚 䛻䛴䛔䛶䜒䚸᪂䛯䛺◊✲䠄䝔䞊䝬䠐䠅䛜䝇䝍䞊䝖䛧䛯䚹㻌
䠐䠅㻌 㻹㼛㼥㼍㼙㼛㼥㼍 ⑓ཎᅉ㑇ఏᏊ 㼙㼥㼟㼠㼑㼞㼕㼚㼚 䛾ᶵ⬟㻌
䝍䞁䝟䜽㉁䛿ṇ䛧䛟ྜᡂ䛥䜜䚸ṇ䛧䛔ᵓ㐀䜢䛸䛳䛶ึ䜑䛶ᮏ
㻌 0R\DPR\D ⑓ࡣ≉࡟᪥ᮏே࡟ከ࠸ࠊ⬻⾑⟶㞀ᐖࢆక࠺⑓
᮶䛾ᶵ⬟䜢Ⓨ᥹䛩䜛䛜䚸䛭䜜䛻䛿✀䚻䛾ศᏊ䝅䝱䝨䝻䞁䛜
Ẽ࡛࠶ࡿࡀࠊࡑࡢཎᅉ㑇ఏᏊࡢ᥈⣴ࢆඹྠ◊✲࡜ࡋ࡚⾜
㔜せ䛺ാ䛝䜢䛧䛶䛔䜛䚹䜎䛯䛔䛳䛯䜣ṇ䛧䛔ᶵ⬟䜢⋓ᚓ䛧䛯䝍
࠸ࠊᕧ኱࡞㑇ఏᏊ P\VWHULQ ࢆࢡ࣮ࣟࢽࣥࢢࡋࡓࠋࡇࡢ㑇
䞁䝟䜽㉁䜒䚸⣽⬊䛻୙᩿䛻䛛䛛䜛✀䚻䛾䝇䝖䝺䝇䛻䜘䛳䛶ኚᛶ
ఏᏊࡢࢥ࣮ࢻࡍࡿࢱࣥࣃࢡ㉁ P\VWHULQ ࡢᶵ⬟ࢆ᫂ࡽ࠿
䛧䛯䜚䚸㑇ఏⓗኚ␗䛻䜘䛳䛶䛹䛖䛧䛶䜒ṇ䛧䛔ᵓ㐀䜢䛸䜜䛺䛔
࡟ࡍࡿࠋ
䝍䞁䝟䜽㉁䜒Ꮡᅾ䛩䜛䚹䛣䛾䜘䛖䛺䛔䜟䜖䜛㻨୙Ⰻ䝍䞁䝟䜽㉁㻪
㻌
䛿䚸༢䛻ᶵ⬟䜢ᣢ䛯䛺䛔䛰䛡䛷䛺䛟䚸⣽⬊ẘᛶ䛻䜘䛳䛶⣽⬊
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
Ṛ䜢ㄏᑟ䛧䚸䜰䝹䝒䝝䜲䝬䞊⑓䜔䝟䞊䜻䞁䝋䞁⑓䛾䜘䛖䛺
䠍䠅㻌 䝁䝷䞊䝀䞁≉␗ⓗศᏊ䝅䝱䝨䝻䞁 㻴㼟㼜㻠㻣 䛾ᶵ⬟ゎᯒ㻌
✀䚻䛾⚄⤒ኚᛶ⑌ᝈ䛾ཎᅉ䛸䜒䛺䛳䛶䛔䜛䚹ᚑ䛳䛶䚸䝍䞁䝟
⫢◳ኚ䜢௦⾲䛸䛩䜛⥺⥔໬⑌ᝈ䛾἞⒪䛻䛚䛔䛶䚸䝁䝷䞊
䜽㉁䜢ṇ䛧䛟ྜᡂ䛩䜛 㼜㼞㼛㼐㼡㼏㼠㼕㼢㼑㻌 㼒㼛㼘㼐㼕㼚㼓 䛸䚸䝭䝇䝣䜷䞊䝹䝗䛧
䝀䞁䛾⏕ྜᡂ䛻ᚲ㡲䛷䛒䜛 㻴㼟㼜㻠㻣 䛿㔜せ䛺๰⸆䝍䞊䝀䝑䝖䛸
䛯䝍䞁䝟䜽㉁䜢㐺ṇ䛻ฎ⌮䛩䜛䛯䜑䛾ရ㉁⟶⌮ᶵᵓ䜢䛸䜒䛹
䛺䛳䛶䛔䜛䚹⫢⮚䛜㞀ᐖ䜢ཷ䛡䜛䛸䚸⫢⣽⬊䛸㢮Ὕෆ⓶⣽⬊
䜒䛻◊✲䛩䜛䛣䛸䛿䚸䝍䞁䝟䜽㉁ືែ䛾ᜏᖖᛶ䚸⣽⬊䝺䝧䝹
䛾㛫䛻Ꮡᅾ䛩䜛⫢ᫍ⣽⬊䛜άᛶ໬䛥䜜䚸ቑṪ䛧䚸䝃䜲䝖䜹䜲
䛷䛾⏕࿨䝅䝇䝔䝮䛾ᜏᖖᛶ䛾⥔ᣢ䛸䛔䛖ほⅬ䛛䜙䛿䚸ᚲ㡲䛾
䞁䜔䝁䝷䞊䝀䞁䜢ศἪ䛩䜛䛣䛸䛷⫢⮚䛾ಟ᚟䛻ᐤ୚䛩䜛䚹ಟ
◊✲㡿ᇦ䛷䛒䜛䚹㻌
᚟ᚋ䚸ቑṪ䛧䛯⫢ᫍ⣽⬊䛿䜰䝫䝖䞊䝅䝇䛻䜘䜚䛭䛾ᩘ䜢ῶᑡ
㻌 ᮏ◊✲ศ㔝䛷䛿ලయⓗ䛻ḟ䛾ㅖⅬ䛻䛴䛔䛶◊✲䜢ᒎ㛤䛧
䛥䛫䚸⫢⮚䛿㏻ᖖ䛾≧ែ䛻ᡠ䜛䛣䛸䛜▱䜙䜜䛶䛔䜛䚹៏ᛶⓗ
䛶䛔䜛䚹㻌
䛺⥺⥔໬䛻䛚䛔䛶䛿䚸⫢ᫍ⣽⬊䛿䝁䝷䞊䝀䞁䜢㐣๫䛻⏘ฟ
㻌
䛧䚸⥺⥔໬䜢㐍⾜䛥䛫䜛䚹ᙜ◊✲ᐊ䛷䛿䚸㻴㼟㼜㻠㻣 䛸䝥䝻䝁䝷䞊
䠍䠅 䝁䝷䞊䝀䞁≉␗ⓗศᏊ䝅䝱䝨䝻䞁 㻴㼟㼜㻠㻣 䛾ᶵ⬟ゎᯒ㻌
䝀䞁䛸䛾┦஫స⏝䜢㜼ᐖ䛩䜛໬ྜ≀䜢⥺⥔໬⑌ᝈ䛾἞⒪䛻
䝁䝷䞊䝀䞁ྜᡂ䛻䛚䛔䛶䝁䝷䞊䝀䞁≉␗ⓗศᏊ䝅䝱䝨䝻䞁
౑䛖䛣䛸䜢┠ⓗ䛸䛧䚸䛭䛾໬ྜ≀䛾᥈⣴䜢⾜䛔䚸᪤䛻໬ྜ≀䜢
㻴㼟㼜㻠㻣 䛿ᚲ㡲䛾ᙺ๭䜢ᯝ䛯䛧䛶䛔䜛䚹䝜䝑䜽䜰䜴䝖䝬䜴䝇䛺䛹䜢
ᚓ䛶䛔䜛㻔≉チฟ㢪῭䜏㻕䚹ᐇ㝿䛻 㻴㼟㼜㻠㻣 䛾ᶵ⬟䜢㜼ᐖ䛧䛯
㥑౑䛧䛶䚸ᮏ◊✲ᐊ䛷Ⓨぢ䛧䛯 㻴㼟㼜㻠㻣 䛾ᶵ⬟ゎᯒ䜢⾜䛖䚹㻌
᫬䛾䚸⫢ᫍ⣽⬊䛾䝍䞊䞁䜸䞊䝞䞊䜢ㄪ䜉䜛஦䛿䚸⥺⥔໬⑌
㻌
ᝈ἞⒪ᡓ␎䜢⪃䛘䜛ୖ䛷ᴟ䜑䛶㔜せ䛷䛒䜛䚹㻌
䠎䠅 ᑠ⬊య䛻䛚䛡䜛䝍䞁䝟䜽㉁ရ㉁⟶⌮ᶵᵓ䛸ᑠ⬊యᜏᖖ
ᛶ⥔ᣢᶵᵓ䛾ゎ᫂㻌
௒ᅇ䚸㻯㼞㼑㻙㻸㼛㼤㻼 䛾䝅䝇䝔䝮䜢⏝䛔䛶䚸䝬䜴䝇䜘䜚༢㞳䛧䛯
⫢ᫍ⣽⬊䛻䛚䛔䛶䚸㻴㼟㼜㻠㻣 䛾䝜䝑䜽䜰䜴䝖䜢⾜䛳䛯䚹䛭䛾⤖ᯝ䚸
ᑠ⬊య䛷䝭䝇䝣䜷䞊䝹䝗䛧䛯䝍䞁䝟䜽㉁䛿䝃䜲䝖䝌䝹䜈㏫㍺
㻴㼟㼜㻠㻣 䜢䝜䝑䜽䜰䜴䝖䛧䛯⫢ᫍ⣽⬊䛷䛿⣽⬊እ䝬䝖䝸䝑䜽䝇䛾䝁
㏦䛥䜜䛶䛛䜙䝴䝡䜻䝏䞁䝥䝻䝔䜰䝋䞊䝮⣔䛻䜘䛳䛶ศゎ䛥䜜䜛
䝷䞊䝀䞁㔞䛜ⴭ䛧䛟ῶᑡ䛧䚸⣽⬊ෆ䛾䝁䝷䞊䝀䞁⵳✚㔞䛜ቑ
䠄䠡䠮䠝䠠䠅䚹䛣䛾㐣⛬䛷㔜せ䛺ᙺ๭䜢ᯝ䛯䛩 㻱㻰㻱㻹 䛚䜘䜃
ຍ䛩䜛䛣䛸䛜☜ㄆ䛥䜜䛯䚹䛣䜜䛻䜘䜛ᑠ⬊య䝇䝖䝺䝇䛿☜ㄆ䛥
㻱㻾㼐㼖㻡 䛸䛔䛖ศᏊ䜢Ⓨぢ䛧䛯䚹䛣䜜䜙䛾ᶵ⬟ゎᯒ䜢⾜䛔䚸ᑠ⬊
䜜䛺䛛䛳䛯䛜䚸䜰䝫䝖䞊䝅䝇䛾䝬䞊䜹䞊䛷䛒䜛䜹䝇䝟䞊䝊䠏䛾
య㛵㐃ศゎᶵᵓ䛾඲ㇺ䜢᫂䜙䛛䛻䛩䜛䚹㻌
ㄏᑟ䛜☜ㄆ䛥䜜䚸㻴㼟㼜㻠㻣 䛜↓䛔䛣䛸䛻䜘䛳䛶⫢ᫍ⣽⬊䛻䜰䝫
㻌
䝖 䞊 䝅 䝇 䛜 ㄏ ᑟ 䛥 䜜 䛶 䛔 䜛ྍ ⬟ ᛶ 䛜 ♧ ၀ 䛥 䜜 䛯 䚹 ௒ ᚋ 䚸
㻌
㻴㼟㼜㻠㻣 㜼ᐖ๣䜢⏝䛔䛯ゎᯒ䜢㐍䜑䛶䛔䛟ணᐃ䛷䛒䜛䚹㻌
䠎 䠅㻌 ᑠ⬊య䛻䛚䛡䜛䝍䞁䝟䜽㉁ရ㉁⟶⌮䚸䝺䝗䝑䜽䝇ไᚚ䚸
䠐䠅㻌 㻹㼛㼥㼍㼙㼛㼥㼍 ⑓ཎᅉ㑇ఏᏊ 㼙㼥㼟㼠㼑㼞㼕㼚㼚 䛾ᶵ⬟㻌
䜹䝹䝅䜴䝮ᜏᖖᛶ䛾䜽䝻䝇䝖䞊䜽䠖ᑠ⬊యᜏᖖᛶ⥔ᣢ䛾ゎ
㻹㼛㼥㼍㼙㼛㼥㼍 ⑓䛾ཎᅉ㑇ఏᏊ䛸䛧䛶䜽䝻䞊䝙䞁䜾䛧䛯 㼙㼥㼟㼠㼑㼞㼕㼚
᫂
䛿䚸ศᏊ㔞⣙ 㻡㻥㻝䡇㻰㼍 䛸䛔䛖ᕧ኱䛺ศᏊ䛷䛒䛳䛯䚹䛧䛛䜒䚸䛣
⣽⬊ෆᑠჾᐁࡢ୍ࡘ࡛࠶ࡿᑠ⬊య࡛ࡣࠊࢱࣥࣃࢡ㉁ရ
䛾ศᏊ䛿䝸䝪䝋䞊䝮䛻㏆䛔኱䛝䛥䛾ᕧ኱䜸䝸䝂䝬䞊䜢స䜚䚸䝎
㉁⟶⌮࣭ࣞࢻࢵࢡࢫไᚚ࣭࢝ࣝࢩ࣒࣓࢘࣍࢜ࢫࢱࢩࢫ࡜
䜲䝙䞁䜔䝥䝻䝔䜰䝋䞊䝮䛻㢮ఝ䛾 㻭㼀㻼 䜰䞊䝊ᆺ䝯䜹䝜䜶䞁䝄
࠸࠺୕ࡘࡢ⎔ቃせᅉࡀᙳ㡪ࢆཬࡰࡋ࠶࠸ࠊᜏᖖᛶࢆ⥔ᣢ
䜲䝮䛸䛧䛶⣽⬊ෆ䛾≀⌮ⓗ䛺㐣⛬䛻ᐤ୚䛧䛶䛔䜛䛷䛒䜝䛖䛣䛸
ࡋ࡚࠸ࡿࠋᡃࠎࡣᑠ⬊య࡛ࢪࢫࣝࣇ࢕ࢻ㑏ඖάᛶ࡟≉໬
䜢᫂䜙䛛䛻䛧䛯䚹䜎䛯䚸㻹㼥㼟㼠㼑㼞㼕㼚 䜢䝊䝤䝷䝣䜱䝑䝅䝳䛷䝜䝑䜽䝎
ࡍࡿ㑏ඖ㓝⣲ (5GM ࢆⓎぢࡋࠊ(5GM ࡀᑠ⬊యࡢࣞࢡࢳ
䜴䞁䛩䜛䛸䚸
ࣥࢱࣥࣃࢡ㉁ ('(0 ࠾ࡼࡧศᏊࢩࣕ࣌ࣟࣥ %L3 ࡜」ྜయࢆ
⾑⟶䛾䜺䜲
ᙧᡂࡍࡿࡇ࡜ࢆぢฟࡋࡓࠋ(5GM ࡣᑠ⬊య࡛ᮎᮇⓗ࡟࣑
䝎䞁䝇䛻␗
ࢫࣇ࢛࣮ࣝࢻࡋࡓศゎᇶ㉁ࡢࢪࢫࣝࣇ࢕ࢻ⤖ྜࢆ⮬㌟ࡢ
ᖖ䛜㉳䛣䜛
㑏ඖάᛶ࡛ษ᩿ࡋࠊᑠ⬊య࠿ࡽࢧ࢖ࢺࢰࣝ࡬ࡢ᤼ฟࢆಁ
䛣䛸䛜᫂䜙
㐍ࡋࠊࢱࣥࣃࢡ㉁ရ㉁⟶⌮࡟࠾࠸࡚㔜せ࡞ᙺ๭ࢆᯝࡓࡋ
䛛䛻䛺䜚䚸
࡚࠸ࡿࡇ࡜ࢆぢฟࡋࡓ㸦58VKLRGD HWDO 6FLHQFH
⑓ែ䛸䛾㛵
0+DJLZDUDHWDO0RO&HOO58VKLRGD
䜟䜚䛾ୖ䛷㔜せ䛺Ⓨぢ䛸䛺䛳䛯䚹⌧ᅾ䚸䛥䜙䛻⤖ྜ䝍䞁䝟䜽㉁
HWDO0RO%LRO&HOO㸧ࠋ
䛺䛹䜢ྵ䜑䛶䚸䛭䛾ᶵ⬟ゎᯒ䜢⾜䛳䛶䛔䜛䚹㻌
ࡉࡽ࡟ (5GM ࡀᑠ⬊య⭷ୖ࡟Ꮡᅾࡍࡿ࢝ࣝࢩ࣒࣏࢘ࣥ
㻌
ࣉ 6(5&$ ࡢࢪࢫࣝࣇ࢕ࢻ⤖ྜࢆ⮬㌟ࡢ㑏ඖάᛶ࡛㛤⿣
㸱㸬Research projects and annual reports
ࡋࠊ」ྜయࢆᙧᡂࡍࡿࡇ࡜࡛ᑠ⬊య࡬ࡢ࢝ࣝࢩ࣒࢘ὶධ
We have been focusing our research on the productive folding
ࢆㄪ⠇ࡋࠊᑠ⬊యࡢ࢝ࣝࢩ࣒࢘ືែ࡟ᙳ㡪ࢆ୚࠼࡚࠸ࡿ
of nascent polypeptides by molecular chaperones and protein
࡜࠸࠺ணഛⓗ࡞ࢹ࣮ࢱࢆᚓ࡚࠸ࡿࠋࡇࡢࡇ࡜ࡣ (5GM ࡢ
quality control mechanism for misfolded proteins within the
㑏ඖຊࡀࢱࣥࣃࢡ㉁ရ㉁⟶⌮ࡢࡳ࡞ࡽࡎࠊᑠ⬊యࡢ࢝ࣝ
cells. Particularly, we have been devoted our activity on the
ࢩ࣒࣓࢘࣍࢜ࢫࢱࢩࢫࡶไᚚࡋࠊࡑࡢࢡࣟࢫࢺ࣮ࢡ࡟㔜
following four major research projects:
せ࡞ᙺ๭ࢆᯝࡓࡍࡇ࡜ࢆព࿡ࡋ࡚࠸ࡿࠋᮏ◊✲ࡣࠊᑠ⬊
యෆ⭍ࡢᜏᖖᛶ⥔ᣢᶵᵓࢆ⌮ゎࡍࡿୖ࡛㔜せ࡛࠶ࡿࠋ 1: Functional analysis of collagen-specific molecular
㻌
chaperone Hsp47.
䠏䠅㻌 䝍䞁䝟䜽㉁ရ㉁⟶⌮䛻䛚䛡䜛ᑠ⬊య䝺䝗䝑䜽䝇䝛䝑䝖㻌
abnormal collagen accumulation in the extracellular matrix of
䝽䞊䜽䛾ព⩏㻌
Liver fibrosis is characterized by
liver. Collagen specific molecular chaperone Hsp47 is
㻌 㻌 ᑠ⬊య䛻䛿䠎䠌✀㢮䜢㉺䛘䜛䜸䜻䝅䝗䝺䝎䜽䝍䞊䝊䠄㓟໬
essential for correct folding and secretion of procollagen. Thus,
㑏ඖ㓝⣲䠅䛜Ꮡᅾ䛩䜛䚹㓟໬㑏ඖ཯ᛂ䛿䚸୍㐃䛾㟁Ꮚఏ㐩
Hsp47 is thought to be potential therapeutic targets for fibrosis.
⤒㊰䛛䜙ᡂ䜛䛜䚸䝥䝻䝔䜸䝭䝑䜽ゎᯒ䠄≉䛻┦஫స⏝ゎᯒ䜢୺
In liver fibrosis, Hepatic Stellate Cells (HSCs) are activated
䛸䛧䛯䜲䞁䝍䞊䝷䜽䝖䞊䝮ゎᯒ䠅䛸㓟⣲㟁ᴟ䛻䜘䜛㓟໬཯ᛂ䛾
and transformed into myofibroblasts which produce collagen
ゎᯒ䚸⾲㠃䝥䝷䝈䝰䞁䠄䠯䠬䠮䠅䜢⏝䛔䛯┦஫స⏝ゎᯒ䛺䛹䜢
actively. It is known that reversion of fibrosis is accompanied
㥑౑䛧䛶䚸ᑠ⬊య䛻䛚䛡䜛୍㐃䛾㓟໬཯ᛂ䛾䜹䝇䜿䞊䝗䜢᫂
by clearance of myofibroblasts by apoptosis. We have already
䜙䛛䛻䛧䛯䚹୰䛷䜒 㻱㼞㼛㻝㼍 䛚䜘䜃䠬䠠䠥䛸䛔䛖䠎䛴䛾㓟໬㓝⣲䛚
found that some of small molecule compounds inhibit the
䜘䜃㓟໬㑏ඖ㓝⣲䛜䝝䝤」ྜయ䜢స䛳䛶䚸ᑠ⬊య䛷䛾㓟໬
interaction between collagen and Hsp47.
཯ᛂ䛻䛚䛡䜛᭱ୖὶ㉳Ⅼ䛻䛺䛳䛶䛔䜛䛸䛔䛖஦ᐇ䜢ぢฟ䛧䛯
For the therapeutic purpose it is important to investigate the
䠄㻷㻚㻌㻭㼞㼍㼗㼕㻌㼑㼠㻌㼍㼘㻚㻘㻌 㻶㻚㻌㻯㼑㼘㼘㻌㻮㼕㼛㼘㻚㻘㻌㻞㻜㻝㻟䠅䚹㻌 㻌 䜎䛯䛣䛾䜘䛖䛺㓟໬
turnover of HSCs under Hsp47 inhibition condition. Here, we
㓝⣲䝛䝑䝖䝽䞊䜽䛻䜘䛳䛶䚸ᑠ⬊యෆ⎔ቃ䛜㓟໬ⓗ䛻ಖ䛯䜜
succeeded in knocking out hsp47 gene by Cre-LoxP system in
䜛䛣䛸䛜䚸ṇᖖ䛺䝍䞁䝟䜽㉁ศἪ䛾䛯䜑䛻ᚲ㡲䛷䛒䜛䛜䚸䛣䛾
isolated HSCs from hsp47 floxed mice. In hsp47-KO HSCs,
䜘䛖䛺䝺䝗䝑䜽䝇ᜏᖖᛶ䛜䚸⚄⤒ኚᛶ⑌ᝈ䜔⪁໬䛻䜘䜚పୗ䛩
we confirmed that immature type 1 collagen is accumulated in
䜛䛣䛸䜢ぢฟ䛧䛯䚹⚄⤒ኚᛶ⑌ᝈ䜔⪁໬䛻䛚䛔䛶䛿⣽⬊㉁䝌
the ER. We also observed the induction of caspase 3, an
䝹䛾䝍䞁䝟䜽㉁ᜏᖖᛶ䛜పୗ䛩䜛䛣䛸䛜▱䜙䜜䛶䛔䜛䛜䚸䛣
apoptosis marker, while we didn’t observe induction of BiP,
䜜䛜⭷䜢㉺䛘䛶ᑠ⬊యෆ⭍䛻ᙳ㡪䜢ཬ䜌䛧䛶䛔䜛䛣䛸䛿㦫䛟
an ER stress inducible protein.
䜉䛝䛣䛸䛷䛒䜚䚸⌧ᅾ䛭䛾䝯䜹䝙䝈䝮䛾ゎ᫂䛻ྲྀ䜚⤌䜣䛷䛔
characterize the hsp47-KO HSCs in terms of the induction of
䜛䚹㻌 㻌
apoptosis.
We are going to further
2: Maintenance of ER homeostasis through the crosstalk
disease called as moyamoya disease. Mysterin with a size of
2+
591kDa contains RING finger domain, which causes a
flux. We identified ERdj5 as a disulfide-reductase in ER.
polyubiquitination of misfolded proteins, and two AAA+ type
ERdj5 forms the supramolecular complex with EDEM and
ATPase domains. Mysterin forms a huge oligomer the size of
BiP, and activates the degradation of proteins misfolded in the
which is comparable to known macromolecules such as the
ER by cleaving the disulfide bonds in terminally misfolded
ribosome and is supposed to exhibit mechanical activity in the
proteins and by facilitating the retrograde transport of these
cell. Thus mysterin is a novel oligomeric AAA+ protein with
proteins from the ER lumen into the cytosol, where they are
RING finger. We preliminary found that knockdown of
degraded by ubiquitin-proteasome system, which is called as
mysterin in zebra fish caused an aberrantly oriented blood
ERAD 䠄R. Ushioda et al., Science 2008; M. Hagiwara et al.
vessels during the development, and would continue such
Mol. Cell 2011; R.Ushioda et al. Mol. Biol. Cell 2013䠅.
functional analysis.
among Protein Quality Control, Redox regulation and Ca
Furthermore, we found that ERdj5 cleaves the disulfide
bond of SERCA2, a Ca2+ pump on ER membrane, and
regulates its function. It suggests that redox activity of ERdj5
㸲㸬ㄽᩥࠊⴭ᭩࡞࡝
is involved not only in protein quality control but also in Ca2+
D. Morito, K. Nishikawa, J. Hoseki, A Kitamura, Y. Kotani, K. Kiso,
homeostasis in the ER. As the ERdj5 is an oxidoreductase in
M. Kinjo, Y. Fujiyoshi & K. Nagata䠖Moyamoya disease-associated
the ER, it is strongly suggested that three important
protein mysterin/RNF213 is a novel AAA+ ATPase, which
homeostasis in the ER, protein, redox and Ca homeostasis, are
dynamically changes its oligomeric state.㻌
cross-talking each other.
Scientific Reports in press
T. Kakugawa, S. Yokota, Y. Ishimatsu, T. Hayashi, S. Nakashima, S.
3. Analysis of ER redox networks in the ER quality control
Hara, N. Sakamoto, H. Kubota, M. Mine, Y. Matsuoka, H. Mukae,
system. More than 20 oxidoreductases have been reported in
K. Nagata & S. Kohno 㸸Serum heat shock protein 47 levels are
the mammalian ER, most of which contain thioredoxin
elevated in acute interstitial pneumonia
domains with CXXC motifs for their enzymatic activity. We
performed the interactome analysis by cloning all of them,
BMC Pulmonary Medicine in press
Y. Honzawa, H. Nakase, M. Shiokawa, T. Yoshino,H. Imaeda, M.
making CXXA mutant of each proteins to stabilize the
Matsuura, Y. Kodama, H. Ikeuchi, A. Andoh,Y. Sakai, K. Nagata,
interaction with downstream proteins, transfecting them and
T. Chiba䠖Involvement of interleukin-17A-induced expression of
immunoprecipitating the associated proteins followed by
heat shock protein 47 in intestinal fibrosis in Crohn’s disease䚹㻌 㻌
identification by mass spectroscopic analysis. We found that
Gut
in press
Ero1a and PDI make a functional and regulatory hub complex,
T. Ramming, H. G. Hansen, K. Nagata, L. Ellgaard, C.Appenzeller-
and successively oxidize other ER-resident oxidoreductases.
Herzog䠖GPx8 peroxidase prevents leakage of H2O2 from the
Such a network consisting of several oxidoreductases,
endoplasmic reticulum㻌 Free Radical Biol Med.
In press
so-called redox network in the ER, is essential for proper
T. Olszak, J. F. Neves, C. M. Dowds, K. Baker, J. Glickman, N. O.
secretion of secretory proteins. We recently revealed that such
Davidson, C-S. Lin, C. Jobin, S. Brand, K. Sotlar, K. Wada, K.
redox network and homeostasis are perturbed by aging and
Katayama, A. Nakajima, H. Mizuguchi, K. Kawasaki, K. Nagata,
abnormal proteins that cause neurodegenerative diseases. It is
W. Müller, S.B. Snapper, S. Schreiber, A. Kaser, S. Zeissig & R. S.
known that proteostasis in the cytosol is impaired by aging
Blumberg䠖Protective mucosal immunity mediated by epithelial
and
neurodegenerative
diseases.
It
is
surprising
that
perturbation of proteostasis in the cytosol leads to impairment
CD1d and IL-10.㻌 㻌 Nature in press
A. Kitamura, N. Inada, H. Kubota, G. Matsumoto, M. Kinjo, R. I.
of redox homeostasis in the ER. We are now elucidating how
Morimoto & K. Nagata䠖Dysregulation of the Proteasome Increases
cytosolic stress interferes the redox homeostasis in the ER
the Toxicity of ALS-linked Mutant SOD1
over the ER membrane.
Genes to Cells in press
T. Kakugawa, S. Yokota, Y. Ishimatsu, T. Hayashi, S. Nakashima, S.
4. Functional analysis of a novel protein, mysterin. We
Hara, N. Sakamoto, Y. Matsuoka, H. Kubota, M. Mine, H. Mukae,
cloned a novel gene encoding a huge protein, and named it as
K. Nagata & S. Kohno䠖Serum heat shock protein 47 levels in
mysterin, which is a causative gene for human steno-occlusive
patients with drug-induced lung disease.
Respiratory Research 14:133(2013)
Kazuhiro Nagata㸸Crosstalk among three different systems of ER
homeostasis. Northwestern University Seminar, Evanston(USA),
T. Kakihana, K. Araki, S. Vavassori, S. Iemura, M. Cortini, C. Fagioli,
2013.07.05
T. Natsume, R. Sitia & K. Nagata䠖'\QDPLFUHJXODWLRQRI(URĮ
and Prx4 localization in the secretory pathway㻌 J. Biol. Chem.
Kazuhiro Nagata㸸From proteostasis to organelle-stasis in the ER.
288(41):29586-29594(2013)
(Plenary Lecture) Gordon Research Conferences ”Stress Proteins
R.Ushioda, J.Hoseki & K. Nagata㸸Glycosylation-independent ERAD
in Growth, Development & Disease”, West Dover(USA),
pathway serves as a backup system under ER stress.
Mol. Biol. Cell.
24(20):3155-3163(2013)
2013.07.07
Kazuhiro Nagata㸸Regulation of collagen synthesis by Hsp47 and
K.Araki, S.Iemura, Y.Kamiya, D.Ron, K.Kato, T. Natsume & K.
P4H in combination with specific inhibitors. Gordon Research
Nagata㸸(URĮ and PDIs constitute a hierarchical electron transfer
Conferences”Collagen”, New London(USA), 2013.07.17
network of endoplasmic reticulum oxidoreductases.
J. Cell. Biol. 202(6):861-874(2013)
Ọ⏣࿴ᏹ㸸ࣉࣟࢸ࢖࣓ࣥ࣍࢜ࢫࢱࢩࢫ࡟࠾ࡅࡿᑠ⬊య࡜ࢧ࢖ࢺ
ࢰࣝࡢࢡࣟࢫࢺ࣮ࢡࠊ➨ 86 ᅇ᪥ᮏ⏕໬Ꮫ఍኱఍ࢩ࣏ࣥࢪ࢘
T. Kakugawa, S. Yokota, Y. Ishimatsu , T. Hayashi, S. Nakashima, S.
࣒ࠊᶓ὾ᕷࠊ2013.09.11
Hara, N. Sakamoto, H. Kubota, M. Mine, Y. Matsuoka, H. Mukae,
K. Nagata & S. Kohno㸸Serum heat shock protein 47 levels are
Kazuhiro Nagata㸸Crosstalk and regulation of ER homeostasis㸸
elevated in acute exacerbation of idiopathic pulmonary fibrosis.
Protein, Redox and Calcium. International Mini
Cell Stress and Chaperones
Simposium”Protein Folding and Disease”, Akita(Japan),
18:581-590(2013)
2013.10.29
T. Fujimori, Y. Kamiya, K. Nagata, K. Kato & N. Hosokawa㸸
Endoplasmic reticulum lectin XTP3-B inhibits endoplasmic
reticulum-DVVRFLDWHGGHJUDGDWLRQRIDPLVIROGHGĮ-antitrypsin
variant. FEBS J. 280(6):1563-1575(2013)
M. F. Abdul-Wahab, T. Homma, M. Wright, D. Olerenshaw,T. R.
Dafforn, K. Nagata & A. D. Miller䠖The pH sensitivity of murine
hsp47 binding to collagen is affected by mutations in the breach
histidine cluster㻌 㻌 J. Biol. Chem. 288(6):4452-4461(2013)
Ꮫ఍Ⓨ⾲
ఀ⸨㐍ஓࠊỌ⏣࿴ᏹ㸸Development of therapeutic small compounds
for fibrotic-diseases by preventing of collagen secretion. AUTM
Asia 2013 Kyoto, Kyoto, 2013.3.20-22
ఀ⸨ 㐍ஓࠊᑠᕝ ᾈ஧ࠊ㧗ᮌ ᇶᶞࠊྜྷ⏣ ᑗேࠊᖹᒣ ᑦᚿ㑻ࠊ
ᗈᕝ ㈗ḟࠊ᪂ᐙ ୍⏨ࠊᅵ஭ 㝯⾜ࠊ஬ᓥ ┤ᶞࠊኟ┠ ᚭࠊỌ
⏣ ࿴ᏹ㸸⥺⥔໬⑌ᝈ἞⒪࡟ྥࡅࡓࢥ࣮ࣛࢤࣥศἪ㜼ᐖ๣ࡢྠ
ᐃ࡜ゎᯒ. ➨65ᅇ᪥ᮏ⣽⬊⏕≀Ꮫ఍኱఍ࠊྡྂᒇᕷࠊ
㸳㸬Ꮫ఍Ⓨ⾲࡞࡝
ᣍᚅㅮ₇ࠊࢩ࣏ࣥࢪ࣒࢘➼ Ọ⏣࿴ᏹ㸸⥺⥔໬⑌ᝈ἞⒪࡟ྥࡅࡓࢥ࣮ࣛࢤࣥศἪ㜼ᐖ๣ࡢ㛤
Ⓨࠊ᪂ᢏ⾡ㄝ᫂఍ࠊᮾிࠊ2036.3.1
Kazuhiro Nagata㸸Crosstalk of proteostasis and redox homeostasis in
the ERࠊThe 1656th Biological Symposiumࠊ୕ᓥᕷࠊ2013.3.5
Kazuhiro Nagata㸸Crosstalk between proteostasis and redox
2013.06.19-21
ᒣᮏ ὒᖹࠊ᱈ཎ ῄࠊᯇᮏ ⨾㤶ࠊబ⸨ ோ⨾ࠊ㛛಴ ᗈࠊỌ⏣ ࿴
ᏹࠊἙ㔝 ᠇஧㸸ᑠ⬊య⭷࡟ᒁᅾࡍࡿ ERAD 」ྜయ࡟ࡼࡿ p62
ไᚚᶵᵓࡢゎᯒ. ➨ 65 ᅇ᪥ᮏ⣽⬊⏕≀Ꮫ఍኱఍ࠊྡྂᒇᕷࠊ
2013.06.19-21
Ryo Ushioda, Kazuhiro Nagata㸸ERdj5, a disulfide reductase in the ER,
regulates Ca2+ momeostasis through the activation of Ca2+ pump,
homeostasis in the ER. Organella Homeostasis Research Center
SERCA2b. Gordon Research Conferences”Stress Proteins in
Kick-off Symposium, Fukuoka, 2013.3.22
Growth, Development & Disease”, West Dover(USA),
Ọ⏣࿴ᏹ㸸ᑠ⬊య࣓࣍࢜ࢫࢱࢩࢫࡢ⥔ᣢᶵᵓࠊࡉࡁࡀࡅࠕࣛ࢖
ࣇࢧ࢖࢚ࣥࢫࡢ㠉᪂ࢆ┠ᣦࡋࡓᵓ㐀⏕࿨⛉Ꮫ࡜ඛ➃ⓗᇶ┙ᢏ
⾡ࠖ◊✲㡿ᇦ➨୍ᅇ㡿ᇦ఍㆟࢔ࢻࣂ࢖ࢨ࣮ㅮ₇ࠊ኱㜰ᕷࠊ
2013.4.9
2013.07.07-12
᳃ᡞ኱௓㸸⬻⾑⟶⑌ᝈࣔࣖࣔࣖ⑓࡟㛵୚ࡍࡿ ATP ࢔࣮ࢮ㸭ࣘࣅ
࢟ࢳ࣮ࣥࣜ࢞ࢮࠊ࣑ࢫࢸࣜࣥࡢᵓ㐀࡜ᶵ⬟. ᪥ᮏ⏕≀≀⌮Ꮫ఍
໭ᾏ㐨ᨭ㒊ㅮ₇఍ࠊᮐᖠᕷࠊ2013.7.8
Kazuhiro Nagata㸸ER stress and protein quality control system in the
Daisuke Morito, Yuri Kotani, Kouki Nishikawa, Jun Hoseki, Satoru
ER. Symposium “The Art of Living with Stress: a Lesson from
Yamazaki, Shun-ichiro Iemura, Toru Natsume, Seiji Takashima,
Ferruccio Ritossa”, Roma(Itary), 2013.04.26
Yoshinori Fujiyoshi, Kazuhiro Nagata㸸Structure and function of
Ọ⏣࿴ᏹ㸸ࢱࣥࣃࢡ㉁ࡢᙧࡀቯࢀࡿ࡜⑓Ẽ࡟࡞ࡿࡗ࡚࣍ࣥࢺ㸽
ி㒔⏘ᴗ኱Ꮫ ๰❧ 50 ࿘ᖺグᛕ஦ᴗࢩ࣏ࣥࢪ࣒࢘ࠗ⣽⬊ෆ
ࡢ᝟ሗ࠿ࡽ་⒪࡟࠾ࡅࡿಶே᝟ሗ࡬࠘ࠊி㒔ᕷࠊ2013.6.29
moyamoya disease-associated AAA+ ATPase/ubiquitin ligase
mysterin. The 35th Naito Conference ‘The Ubiquitin Proteasome
System’, Sapporo(Japan), 2013.7.10㸦ཱྀ㢌࣭࣏ࢫࢱ࣮Ⓨ⾲㸧
Ishimatsu,Shota Nakashima,Shintaro Hara,Noriho
Shoshiro Hirayama, Shun-ichiro Iemura, Kazutaka Araki, Daisuke
Morito, Toru Natsume, Shigeo Murata, Kazuhiro Nagata㸸A new
Sakamoto,Hiroshi Kubota,Yasuhiro Matsuoka,Kazuhiro Nagata and
mechanism of nuclear export of ubiquitinated proteins by the
Shigeru Kohno㸸
th
UBIN-POST system. The 35 Naito Conference ‘The Ubiquitin
Serum heat shock protein 47 levels are elevated in acute interstitial
Proteasome System’, Sapporo(Japan), 2013.7.10㸦࣏ࢫࢱ࣮Ⓨ⾲㸧
pneumonia. 18th Congress of the Asian Pacific Society of
Respirology, Yokohama, 2013.11.11-14
Kunito Kawasaki, Kazuo Ikeda, Ryo Ushioda, Kazuhiro Nagata㸸
ER-stress-mediated apoptotic cell death in Hepatic stellate cells:
ᑠ㇂཭⌮ࠊ᳃ᡞ኱௓ࠊᒣᓮᝅࠊ㧗ᓥᡂ஧ࠊᖹ⏣ᬑ୕ࠊỌ⏣࿴ᏹ㸸
Effect of deletion of collagen specific molecular chaperone Hsp47
ࡶࡸࡶࡸ⑓㛵㐃ࢱࣥࣃࢡ㉁ Mysterin ࡟ࡼࡿ zebrafish ࡢⓎ⏕ไ
gene in mice. Gordon Research Conferences”Collagen”, New
ᚚ. ➨ 8 ᅇ⮫ᗋࢫࢺࣞࢫᛂ⟅Ꮫ఍኱఍ࠊᯇᮏᕷࠊ2013.11.15㸦ཱྀ
㢌Ⓨ⾲㸧㸦ⱝᡭ◊✲ዡບ㈹ೃ⿵㸧
London(USA), 2013.07.14-19
Shinya Ito, Koji Ogawa, Motoki Takagi, Akihito Yoshida, Takatsugu
᳃ᡞ኱௓ࠊすᕝᖾᕼࠊᐆ㛵῟ࠊ໭ᮧᮁࠊᑠ㇂཭⌮ࠊኟ┠ᚭࠊ㔠
Hirokawa, Shoshiro Hirayama, Kazuo Shin-ya, Takayuki Doi,
ᇛᨻᏕࠊ⸨ྜྷዲ๎ࠊỌ⏣࿴ᏹ㸸ࣔࣖࣔࣖ⑓ࢱࣥࣃࢡ㉁࣑ࢫࢸ
Naoki Goshima, Tohru Natsume, Kazuhiro Nagata㸸Inhibition of
ࣜࣥࡢືⓗ」ྜయᙧᡂ࡜⣽⬊ෆᶵ⬟. ➨ 36 ᅇ᪥ᮏศᏊ⏕≀Ꮫ
఍ᖺ఍࣮࣡ࢡࢩࣙࢵࣉࠊ⚄ᡞᕷࠊ2013.12.3-6㸦ཱྀ㢌Ⓨ⾲㸧
collagen-specific molecular chaperone Hsp47 with small molecules.
Gordon Research Conferences”Collagen”, New London(USA),
₻⏣ுࠊᐑᮏ❶ṓࠊ⚟⏣ὈᏊࠊ⸨஭ၐᖹࠊᚚᏊᰘඞᙪࠊỌ⏣࿴
ᏹ㸸ERdj5, a disulfide reductase in the ER, regulates Ca2+
2013.07.14-19
homeostasis through the activation of Ca2+ pump, SERCA2b.
Tomoyuki Kakugawa, Shin-ichi Yokota, Yuji Ishimatsu, Tatsuhiko
Harada, Shota Nakashima, Shintaro Hara, Noriho Sakamoto,
CREST-ࡉࡁࡀࡅᵓ㐀⏕࿨⛉Ꮫ㡿ᇦ࢟ࢵࢡ࢜ࣇ࣑࣮ࢸ࢕ࣥࢢࠊ
Hiroshi Kubota, Mariko Mine, Yasuhiro Matsuoka, Hiroshi Mukae,
Ᏺཱྀᕷࠊ2013.12.26
Kazuhiro Nagata and Shigeru Kohno㸸Serum heat shock protein 47
᳃ᡞ኱௓ࠊᑠ㇂཭⌮ࠊすᕝᖾᕼࠊ໭ᮧᮁࠊᒣᓮᝅࠊ㔠ᇛᨻᏕࠊ
levels in patients with drug induced lung diseases. European
㧗ᓥᡂ஧ࠊᖹ⏣ᬑ୕ࠊ⸨ྜྷዲ๎ࠊỌ⏣࿴ᏹ㸸ࣔࣖࣔࣖ⑓ࢱࣥ
Respiratory Society Annual Congress,Barcelona(Spain),
ࣃࢡ㉁࣑ࢫࢸࣜࣥࡢᵓ㐀࡜ᶵ⬟. CREST-ࡉࡁࡀࡅᵓ㐀⏕࿨⛉
2013.9.7-11
Ꮫ㡿ᇦ࢟ࢵࢡ࢜ࣇ࣑࣮ࢸ࢕ࣥࢢࠊᏲཱྀᕷࠊ2013.12.26
Kazuhiro Nagata, Daisuke Morito (Speaker), Yuri Kotani㸸Mysterin,
ᒣᮏὒᖹࠊỌ⏣࿴ᏹ㸸᪂つ࣮࢜ࢺࣇ࢓ࢪ࣮㛵㐃ᅉᏊ DNAJC16
ࡢᶵ⬟ゎᯒ. CREST-ࡉࡁࡀࡅᵓ㐀⏕࿨⛉Ꮫ㡿ᇦ࢟ࢵࢡ࢜ࣇ࣑
the largest molecule of AAA+ ATPase family members with E3
࣮ࢸ࢕ࣥࢢࠊᏲཱྀᕷࠊ2013.12.26
ubiquitin ligase activity, is involved in development of zebrafish
EMBO workshop”AAA+ proteins:from mechanism and disease to
ఀ⸨㐍ஓࠊᑠᕝ ᾈ஧ࠊ➉ෆ ᜏࠊ஬ᓥ ┤ᶞࠊኟ┠ ᚭࠊỌ⏣ ࿴
ᏹ㸸⥺⥔໬⑌ᝈ἞⒪࡟ࡴࡅࡓࢥ࣮ࣛࢤࣥ≉␗ⓗศᏊࢩࣕ࣌ࣟ
targets”, Neuss( Germany), 2013.9.15-19㸦ཱྀ㢌Ⓨ⾲㸧
ࣥ Hsp47 ࡢ┦஫స⏝㜼ᐖ๣ࡢྠᐃ. CREST-ࡉࡁࡀࡅᵓ㐀⏕࿨
Daisuke Morito, Kouki Nishikawa, Jun Hoseki, Akira Kitamura, Yuri
⛉Ꮫ㡿ᇦ࢟ࢵࢡ࢜ࣇ࣑࣮ࢸ࢕ࣥࢢࠊᏲཱྀᕷࠊ2013.12.26
Kotani, Masataka Kinjo, Yoshinori Fujiyoshi and Kazuhiro Nagata㸸
Protential dynamic equilibrium of moyamoya disease-associated
᳃ᡞ኱௓㸸Structure and Function of Moyamoya Disease
AAA+ ATPase mysterin. EMBO workshop”AAA+ proteins:from
Susceptibility Protein Mysterin/RNF213. ➨ 1724 ᅇࣂ࢖࢜ࣟࢪ࢝
mechanism and disease to targets”,Neuss( Germany),2013.9.15-19
ࣝࢩ࣏ࣥࢪ࣒࢘ࠊᅜ❧㑇ఏᏛ◊✲ᡤࠊ୕ᓥᕷࠊ2014.1.29
Daisuke Morito㸸Structure and function of moyamoya
disease-associated AAA+ ATPase/ubiquitin ligase
mysterin/RNF213. Max Plank Institute Seminar, Martinsried
㸴㸬ࡑࡢ௚≉グ஦㡯 (Germany), 2013.9.21㸦ཱྀ㢌Ⓨ⾲㸧
㸯㸧እ㒊㈨㔠 Ryo Ushioda and Kazuhiro Nagata㸸ER homeostatic mechanism
through disulfide reductase ERdj5. ➨ 8 ᅇᑠ⬊యࢫࢺࣞࢫ◊✲఍ࠊ
㔠ἑᕷࠊ2013.10.25-26
ᇉⰼኴ୍ࠊ᪂ᮌ࿴Ꮥࠊ6WHIDQR9DYDVVRULࠊᐙᮧಇ୍㑻ࠊ0DUJKHULWD
⚾❧኱Ꮫᡓ␎ⓗ◊✲ᇶ┙ᙧᡂᨭ᥼஦ᴗ◊✲
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◊✲ศᢸ⪅㸸Ọ⏣࿴ᏹࠊྲྀᚓᖺᗘ㸸+ ᖺ ᖺ
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Human Frontier Science Program㸦㹆㹄㹑㹎㸧
ᏹ㸸'\QDPLFUHJXODWLRQRI(URȘDQG3HUR[LUHGR[LQ
ㄢ㢟ྡ㸸Cell Stress and Proteostasis Dysfunction in Aging and
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Diseaseࠊ◊✲ศᢸ⪅㸸Ọ⏣࿴ᏹࠊྲྀᚓᖺᗘ㸸+ ᖺ ᖺ༙
ࣞࢫ◊✲఍ࠊ㔠ἑᕷࠊ
Yoshitsugu Higashi,Tomoyuki Kakugawa,Shin-ichi Yokota,Yuji
⛉Ꮫ◊✲㈝⿵ຓ㔠࣭ᇶ┙◊✲㹑
ㄢ㢟ྡ㸸ࣞࢻࢵࢡࢫไᚚ࡟ࡼࡿᑠ⬊యᜏᖖᛶ⥔ᣢᶵᵓࡢ◊✲ࠊ
Ọ⏣࿴ᏹ㸸᪥ᮏᏛ⾡఍㆟㸦⣽⬊⏕≀Ꮫ㸧㐃ᦠ఍ဨ
◊✲௦⾲⪅㸸Ọ⏣࿴ᏹࠊྲྀᚓᖺᗘ㸸+ ᖺ ᖺ
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Ọ⏣࿴ᏹ㸸ᩥ㒊⛉Ꮫ┬ ⛉Ꮫ◊✲㈝⿵ຓ㔠ᑂᰝጤဨ㸦ᇶ┙㹑㸧
⛉Ꮫᢏ⾡᣺⯆ᶵᵓ㹁㹐㹃㹑㹒ࠕࣛ࢖ࣇࢧ࢖࢚ࣥࢫࡢ㠉᪂ࢆ┠ᣦ
Ọ⏣࿴ᏹ㸸ᡓ␎ⓗ๰㐀◊✲᥎㐍஦ᴗ㸦ࡉࡁࡀࡅ㸧◊✲㡿ᇦࠕࣛ
ࡋࡓᵓ㐀⏕࿨⛉Ꮫ࡜ඛ➃ⓗᇶ┙ᢏ⾡ࠖ
ㄢ㢟ྡ㸸ᑠ⬊యᜏᖖᛶ⥔ᣢᶵᵓ㸸5HGR[&D
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ůŒ èà ijÏIJĬęĭ°cł¨īĩĕĢŀķĮIJŌŪ
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Cell growth signal
ERK
Cell cycle control signal
cdk1/cyclinB
Signal integration
Signal feedback
GM130/GRASP65/p115
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Ø ïþóû ”ŸijŌŪŐĴ ćï wĥĿĢįIJļīĭÖ
Cell polarization
Directed cell movement
Cell cycle progression
Fig. 1. Golgi appoints as a platform of signal transduction
The Golgi apparatus changes its structure and localization in
response to the cell growth signal and the cell cycle control
signal. Conversely, the information of the structure and the
function of the Golgi apparatus feedback to the signal
transduction pathway.
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IJļīĭC ğ¼ ĢģŀĭęĿĢįĞ„ ( ģŀĩŰS Š
the regulation of the cell polarization and cell growth.
űĕØ
However, the regulatory mechanism remains obscure.
Under this circumstance, we are trying to elucidate the
siControl
siPAFAH1B3
regulatory mechanism of the structure and the function
Cont pH
of the Golgi apparatus to understand how Golgi
apparatus control cellular polarization and movement.
GM130 is a cytoplasmic peripheral membrane protein
(a Golgi matrix protein) localized at the Golgi apparatus
that was found and reported by Nakamura et al. on 1995
(N. Nakamura et al. J Cell Biol, 131, p1715 1995). It
Low pH
binds to p115 and GRASP65 and plays essential role for
the cisternal stacking. It also plays an important role in
the regulation of cell growth, motility and polarization.
Under these circumstances, we have been analyzing the
function of GM130 and its binding proteins to obtain key
Fig. 2 Knockdown of PAFAH1B3
protect the Golgi apparatus from
disassembly under low pH.
information for understanding the regulatory mechanism
of the Golgi structure and function and also the
mechanism for the regulation of cellular functions by the
Golgi apparatus.
Research projects and annual reports
During the development of embryo or tissues, and
We are now focusing on (1) the structural analysis of
cellular differentiation, the cell has to acquire polarity to
GM130 molecule, (2) the developmental analysis of
deliver cell adhesion molecules and inducing factors to
GM130 functions using zebrafish as a model organism,
specific directions. The cell also has to acquire front and
(3) analysis of the molecular mechanism of the Golgi
rear polarity when it moves to a proper direction.
disassembly by low pH treatment and (4) analysis of the
Secretory pathway plays important roles to enable the
function of YIPF proteins.
polarization of cells by regulating the delivery of
This year, we have analyzed the role of phospholipase
proteins and lipids. The Golgi apparatus is especially
A2 in the Golgi disassembly by low pH treatment. It was
important core organelle in the secretory pathway. Thus,
reported that cPLA2α (PLA2G4), iPLA2γ (PLA2G6) and
the structure, function and location of the Golgi
PAFAHIb (PAFAH1B) were involved in the structural
apparatus
and functional maintenance of the Golgi apparatus.
play
essential
roles
to
support
proper
polarization of the cells.
PAFAHIb is composed of three subunits (B1, B2, B3)
The secretory pathway has to be activated to support
while other PLA2s are a single molecule. All of these
active cell growth. In fact, we have shown that the Golgi
PLA2s are reported to induce tubules from the Golgi
apparatus functions as a platform of the growth signal
apparatus and function to fuse with other Golgi
transduction and cell cycle control and controls the
fragments or with other secretary pathway organelles.
activity of the secretory pathway in response to the
We tried to knockdown these PLA2s and found that only
growth signal. Golgi apparatus receives the growth
PAFAH1B3 knockdown showed protection of the Golgi
signal via ERK pathway and also the cell cycle control
apparatus from fragmentation at the low pH (Fig. 2).
signal via CDK pathway, and changes its shape and
Surprisingly, knockdown of other subunit of PAFAHIb
location in the cell. Conversely, the information of the
did not protect the Golgi disassembly. Therefore, it was
activity of the Golgi apparatus may provide feedback to
suggested
the signal transduction pathways (Fig. 1: N. Nakamura,
fragmentation in a B3 subunit dependent manner.
that
et al., Curr. Opin. Cell Biol., 2012).
As described above, the structure and the function of
the Golgi apparatus are suggested to play active roles for
:7643
Ø ıĤØ
PAFAHIb
induces
the
Golgi
;743Ø
Jeerawat Soonthornsit, Ryuichi Ishida, Nobuhiro Nakamura. Yip1
domain family members localizing in the trans-Golgi/ transGolgi network. 2013 "Molecular Membrane Biology" Gordon
Research Conference, Proctor Academy, Andover, NH, USA.
2013.7.14-19
Yoko Yamaguchi, Daisuke Tamura, Jeerawat Soonthornsit,
Ryuichi Ishida, andØ Nobuhiro Nakamura. Low cytoplasmic pH
reduces ER-Golgi trafficking and induces disassembly of the
Golgi apparatus in a phospholipase A2 dependent manner. Golgi
Symposium 2013, Bad Ischl, Austria. 2013.9.17-19
‚zŽŲa^6.Ø GM130¬"ijhÅ°cų36)\`
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ĥºIJĕĮĴą >šħĄēĦŇŖŒńŎĥIĕĠ¶_
ĸ¢ėēĢĎIJĄöαó ĸĕě£°×ďĕĠĊĴē
development, and also trying to understand a genetic program
that globally organizes the circuit formation in the brain. To
approach these problems, we employ a small brain of
Drosophila, which comprises 105 neurons, only a millionth
the size of a human brain. Our research, based on the analysis
of the mutants that show either a behavioral or morphological
phenotype, is currently focused on the mechanisms for
synaptic differentiation.
Ģď¢4ĔĵĴąēĦēĢħĄ >šĥčĊĠ öαó Ħ
Research Project:
M9ÝďŽLĕĠĊĴěĮĥ—ĖĠĊĴ-¸_ďĉĴąë
A role for Hig protein in the synaptic clefts.
The hig (hikaru geneki) gene, identified by a mutant
phenotype of reduced locomotor activity (Hoshino et al.,
Neuron 1993), encodes a protein localized to the synaptic
clefts in the brain (Hoshino et al., Development 1996). The
goal of this project is to reveal roles for Hig and other matrix
proteins in the synaptic clefts. In addition, the absence of one
of the human proteins resembling to Hig is known to cause
epilepsy, mental retardation and brain malformation. One of
our research aims is to reveal the functional relationships
between Hig and the human protein.
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Őŋō öαó Ģ öαô čıĨÑ<ʼnťŔĿÏ öù÷ ĦM9ĸ
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ŔĿÏĦ¡¨ħĄ{¡¨ďĮĠĦġĉijĄēĦÜ
ĥĻťŔĿōĸįěIJėēĢďzWĔĵĴąë
ĤčĄŇŖŒńŎĥIėĴ¶_FéčıĨńŘţŋńŦ
>šĦäĥğĊĠħĄŭ6—Ħ|.U1Ą|Ÿƒ
1ďęĵĚĵAĐĤ͕ĸĕĠđĵěąë
U… Hig ,BFN
Ra/6<1~[
V$#!Dig `t$Hig !/
6<1^{$
DLG
[V&d$H
fAchR -;?724
[V&Oz$
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74Research projects and annual reports
How the brain expresses a variety of neural function still
remains enigmatic. We are studying molecular mechanisms
underlying neuronal events that occur during nervous system
Annual reports:
A matrix protein Hikaru genki localizes to the cholinergic synaptic
clefts and regulates the postsynaptic organization in the Drosophila
brain
The synaptic cleft is a crucial space for neurotransmission and
serves as an interface that provides extracellular scaffolds and
signals for the differentiation or maintenance of presynaptic and
postsynaptic terminals. Albeit a number of molecules that
constitute either terminals have been studied, little is known about
the proteins that are present in the synaptic cleft matrix, especially
in the central nervous system (CNS). We report that Hikaru
genki (Hig), a secreted protein with an Ig motif and CCP
(Complement Control Protein) domains, localizes specifically to
the synaptic clefts of cholinergic synapses in the Drosophila CNS.
Our data indicate that this specific localization of Hig is achieved
by trapping of secreted and diffused Hig to the synaptic clefts
even when it is ectopically expressed in non-cholinergic neurons
and glia. Notably, in the absence of Hig, an intracellular scaffold
protein DLG was abnormally accumulated in the cholinergic
postsynapses, while the synaptic distribution of acetylcholine
receptor (AchR) subunits Dα6 and Dα7 were significantly
decreased. Consistently, the hig mutant flies showed resistance
to an AchR agonist, spinosad, which causes lethality by activating
specifically Dα6 among AchR subunits, suggesting that the loss
of Hig compromises the synaptic activity mediated by Dα6.
These results indicate that Hig is a specific component of synaptic
cleft matrix for cholinergic synapses and regulates the
postsynaptic organization in the CNS.
84/!+" 94(, Hikaru genki protein, localized to the synaptic clefts, is required
for the normal function of cholinergic synapses.
Minoru Nakayama and Chihiro Hama
ª 36 6w{B—“DSîë £fOîë2013. 12.3 - 6 ë
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⢾㉁⏕≀Ꮫ◊✲ᐊᩍᤵ ⚟஭ ᡂ⾜
Laboratory of Glycobiology Prof. Shigeyuki Fukui,Ph.D
㸯㸬◊✲ᴫせ
⢾㙐ࡣཎ᰾⣽⬊࡜┿᰾⣽⬊࡟ᗈࡃᏑᅾࡍࡿከᵝ࡞᝟
ሗࢆᣢࡘศᏊ࡛ࠊ⢾ࢱࣥࣃࢡ㉁ࠊ⢾⬡㉁ࠊࣉࣟࢸ࢜ࢢࣜ
࢝ࣥ࡜ࡋ࡚Ꮡᅾࡍࡿࠋ⢾㙐ࡢᢸ࠺⏕≀Ꮫⓗ࡞ᙺ๭ࡣࡇࢀ
ࡲ࡛ࡢከࡃࡢ◊✲࠿ࡽࠊࢱࣥࣃࢡ㉁㧗ḟᵓ㐀ࡢ┘ど
ࡓࡵ࡟ࠊ࣏ࣜࣛࢡࢺࢧ࣑ࣥ㙐ࡢⓎ⌧㔞ࡀᑡ࡞࠿ࡗࡓࡇ
࡜ࡀ᫂ࡽ࠿࡜࡞ࡗࡓࠋ
㸦quality control㸧ࠊ⬇Ⓨ⏕ࡢึᮇࡢࢥࣥࣃࢡࢩࣙࣥ࡟
CD24 ࡣࡇࢀࡲ࡛ࡢከࡃࡢ◊✲࠿ࡽࠊච␿⣔㸦≉࡟ᮍศ
௦⾲ࡉࢀࡿ⣽⬊㛫ࡢ᥋╔ࠊච␿⣔⣽⬊ࡢ⾑⟶⣔࠿ࡽࣜࣥ
໬ B-⣽⬊㸧ࠊ⚄⤒⣔⣽⬊ࡸ࠸ࡃࡘ࠿ࡢ⒴໬⣽⬊࡞࡝࡟Ⓨ
ࣃ⣔࡬ࡢ⛣ື࡟㛵ࢃࡿࢭࣞࢡࢳࣥࡀ⢾㙐ࢆ㆑ูࡍࡿࡇ࡜ࠊ
⌧ࡉࢀࡿࡇ࡜ࡀ▱ࡽࢀࠊࡲࡓࠊSDS-PAGE ୖࡢ≉␗࡞⾜
ከࡃࡢ࣍ࣝࣔࣥ㸦FGF ࡸ HGF ࡞࡝㸧࡜⣽⬊ቑṪᅉᏊࡀ
ື࡟ࡘ࠸࡚ሗ࿌ࡉࢀ࡚࠸ࡓࡀࠊࡑࡢཎᅉࡢࡳ࡞ࡽࡎࠊ⏕
ࡑࢀࡽࡢཷᐜయ࡜⤖ྜࡋ࡚⏕ࡌࡿࢩࢢࢼࣝఏ㐩ࢆ⢾㙐ࡀ
≀Ꮫⓗ࡞ᙺ๭࡟ࡘ࠸࡚ࡶ୙᫂࡜ࡉࢀ࡚࠸ࡿࠋ
ㄪ⠇ࡋ࡚࠸ࡿࡇ࡜ࠊච␿⣔⣽⬊ࡢࣜࢡ࣮ࣝࢺࡸάᛶ໬࡟
᭱㏆ࠊ⢾㙐࡜┦஫స⏝ࡍࡿࢱࣥࣃࢡ㉁ࡢࣜ࢞ࣥࢻ࡜࡞
㛵ࢃࡿࢣࣔ࢝࢖ࣥࡸࢧ࢖ࢺ࢝࢖ࣥࡢᒁᡤ㒊఩࡬ࡢ⵳✚ࠊ
ࡿ⢾㙐ᵓ㐀ࢆ᳨⣴ࡍࡿ᪉ἲ࡜ࡋ࡚ࠊேᕤ⢾⬡㉁㸦ࢿ࢜ࢢ
ឤᰁ࢘࢖ࣝࢫࡢ docking site ࡢᙧᡂࠊ࡞࡝࡟⢾㙐ࡀ῝ࡃ
ࣛ࢖ࢥࣜࣆࢻ㸧ࢆᛂ⏝ࡋࡓ⢾㙐࣐࢖ࢡࣟ࢔ࣞ࢖ἲࢆ⪃᱌
㛵ࢃࡿࡇ࡜ࡀ᫂ࡽ࡟ࡉࢀ࡚࠸ࡿࠋࡲࡓࠊ⣽⬊ࡢࡀࢇ໬࡟
ࡋࠊ㧗ឤᗘ࡛⤖ྜ⢾㙐ࡢᵓ㐀ࢆ᥎ᐃࡍࡿࡇ࡜ࢆྍ⬟࡜ࡋ
కࡗ࡚Ⓨ⌧ࡉࢀࡿ≉␗⢾㙐ࡶ᫂ࡽ࠿࡜ࡉࢀࠊࡀࢇ⣽⬊ࡢ
ࡓࠋ
ቑṪ࡜㌿⛣࡜ࡢ㛵ࢃࡾ࡟ࡘ࠸࡚ࡶὀ┠ࡉࢀ࡚࠸ࡿࠋࡋ࠿
ࡑࡇ࡛⌧ᅾࡣࠊ1㸧CD24 ࡀ⒴⣽⬊ࢆྵࡵ࡚ᮍศ໬⣽⬊
ࡋ࡞ࡀࡽࠊ⣽⬊᥋╔࣭ㄆ㆑ࡸ⣽⬊ቑṪ࡞࡝࡟㛵ࢃࡿከࡃ
࡟Ⓨ⌧ࡉࢀࡿࡇ࡜࠿ࡽࠊCD24 ࡢⓎ⌧ࢆᢚไࡋࡓ᫬ࡢศ
ࡢࢱࣥࣃࢡ㉁ࡀ࡝ࡢࡼ࠺࡞≉␗⢾㙐ᵓ㐀࡜┦஫స⏝ࡋ࡚
໬㐣⛬࡬ࡢᙳ㡪࡟⯆࿡ࡀᣢࡓࢀࡿࠋࡑࡇ࡛ࠊRNAi ἲࢆ
⏕⌮άᛶࡀㄪ⠇ࡉࢀ࡚࠸ࡿࡢ࠿࡟ࡘ࠸࡚ࡣ୙᫂࡞Ⅼࡀከ
⏝࠸࡚ PC12 ⣽⬊ࡢ CD24 Ⓨ⌧ࢆᢚไࡉࡏ࡚ NGF ่⃭
ࡃṧࡉࢀ࡚࠸ࡿࠋ
࡟ࡼࡿ PC12 ⣽⬊ࡢࢽ࣮ࣗࣟࣥ࡬ࡢศ໬ࡢᙳ㡪ࢆほᐹࡍ
ࡇࢀࡲ࡛⢾㙐ࡢព⩏࡟㛵ࡍࡿ◊✲ࢆ⥆ࡅ࡚ࡁࡓࡀࠊ᭱
ࡿࠋࡲࡓࠊNGF ࡢཷᐜయ⤖ྜ࡟ࡼࡿࢩࢢࢼࣝఏ㐩࡟ཬࡰ
㏆ࡢᮎᲈ⚄⤒⣽⬊(PC12,PC12D ⣽⬊)ࡢࢽ࣮ࣗࣟࣥ࡬ࡢ
ࡍ CD24 ࡢᙺ๭ࡶ㏣ཬࡍࡿࠋ2㸧࣏ࣜࣛࢡࢺࢧ࣑ࣥ㙐௨እ
ศ໬࡟㛵ࢃࡿ⢾㙐ᵓ㐀ࡢẚ㍑◊✲࠿ࡽࠊᮍศ໬㸦NGF ↓
࡟ࠊCD24 ศᏊୖ࡟ࡣᵝࠎ࡞⢾㙐ࡀ⤖ྜࡋ࡚࠸ࡿࠋࡑࢀ
่⃭㸧≧ែ࡟࠶ࡿ PC12 ⣽⬊࡟࠶ࡗ࡚ࡣࠊ⣽⬊⭷⾲㠃࡟
ࡽ⢾㙐ࡢᙺ๭ࢆ㏣ཬࡍࡿࡓࡵ࡟ࠊCD24 ࠿ࡽศ㞳ࡋࡓ⢾
࠶ࡿ⢾ࢱࣥࣃࢡ㉁࡟⤖ྜࡋ࡚࠸ࡿ࣏ࣜࣛࢡࢺࢧ࣑ࣥ㙐ࡢ
㙐ࢆࢿ࢜ࢢࣛ࢖ࢥࣜࣆࢻ໬ࡋࠊ⢾㙐࣐࢖ࢡࣟ࢔ࣞ࢖ἲ࡟
Ⓨ⌧㔞ࡀࢽ࣮ࣗࣟࣥ࡬࡜ศ໬ࡍࡿ㐣⛬࡛ᢚไࡉࢀࡿࡇ࡜ࠋ
ᛂ⏝⏝ࡋ࡚ࠊCD24 ศᏊୖࡢᵝࠎ࡞⢾㙐ࡢᵓ㐀ࢆ᫂ࡽ࠿
ࡲࡓࠊ⯆࿡῝࠸ࡇ࡜࡟ࠊPC12 ⣽⬊࠿ࡽኚ␗⣽⬊࡜ࡋ࡚
࡟ࡍࡿ࡜࡜ࡶ࡟ࠊࡑࢀࡽ⢾㙐ࠊ≉࡟࣏ࣜࣛࢡࢺࢧ࣑ࣥ⢾
ศ㞳ࡉࢀࡓ PC12D ⣽⬊࡛ࡣࠊNGF ࡟཯ᛂᛶࡀ㧗ࡃࠊ▷
㙐࡜┦஫స⏝ࡍࡿ⏕య≀㉁ࢆྠᐃࡍࡿࠋ3㸧ච␿⣔ࡢ B-
᫬㛫࡛ࢽ࣮ࣗࣟࣥ࡬࡜ศ໬ࡍࡿ⬟ຊࢆഛ࠼࡚࠸ࡿࡇ࡜࡜ࠊ
⣽⬊࡟㛵ࡋ࡚ࠊ㫽㢮࡛ࡣ㦵㧊࡛⏕ࡲࢀࡓᮍ⇍ B-⣽⬊ࡣ⥲
࣏ࣜࣛࢡࢺࢧ࣑ࣥ㙐ࡢⓎ⌧㔞ࡢῶᑡ࡜ࡀࡼࡃ୍⮴ࡋࡓࠋ
᤼ἥ⭍ࡢᮎ➃࡟࠶ࡿࣇ࢓ࣈࣜ࢟࢘ࢫᄞ࡛ศ໬ቑṪࡋ࡚ᡂ
ࡑࡇ࡛ࠊ࣏ࣜࣛࢡࢺࢧ࣑ࣥ㙐ྵ᭷⢾ࢱࣥࣃࢡ㉁ࢆ PC12
⇍ B-⣽⬊࡜࡞ࡿࡇ࡜ࡀ▱ࡽࢀ࡚࠸ࡿࠋ᪂ᆺ㫽࢖ࣥࣇ࢚ࣝ
⣽⬊ࡢ⭷⏬ศ࠿ࡽศ㞳⢭〇ࡋࠊࡑࡢ୺せ࡞⢾ࢱࣥࣃࢡ㉁
ࣥࢨ◊✲ࡢ୍ࡘ࡜ࡋ࡚ࠊ࢖ࣥࣇ࢚ࣝࣥࢨ࢘࢖ࣝࢫࡢឤᰁ
ࡢ 1 ࡘ࡟ࡘ࠸࡚ࠊ࢔࣑ࣀ㓟㓄ิศᯒࡢỴᐃࠊ㑇ఏᏊࢹ࣮
ࡍࡿᐟ୺⣽⬊ࡢ 1 ࡘ࡛ࠊච␿⣔࡟ᙳ㡪ࢆ୚࠼ࡿᶆⓗ⢾ࢱ
ࢱ࣮࣮࣋ࢫࡢ᳨⣴ࠊ࣏ࣜࣛࢡࢺࢧ࣑ࣥศゎ㓝⣲࡟ࡼࡿࢱ
ࣥࣃࢡ㉁࡜ࡋ࡚ࡶ CD24 ࡀ⪃࠼ࡽࢀࡓࠋࡑࡇ࡛ࠊࢽ࣡ࢺ
ࣥࣃࢡ㉁ࡢᣲືࡢほᐹ࡞࡝࠿ࡽࠊ୺せ࡞࣏ࣜࣛࢡࢺࢧ࣑
ࣜࡢࣇ࢓ࣈࣜ࢟࢘ࢫᄞ࡟࠶ࡿ B-⣽⬊࡟ᑐࡋ࡚ࡢ࢖ࣥࣇࣝ
ࣥྵ᭷⢾ࢱࣥࣃࢡ㉁ࡢ 1 ࡘࡀ CD24 ࡛࠶ࡿࡇ࡜ࡀ✺ࡁṆ
࢚ࣥࢨ࢘࢖ࣝࢫࡢឤᰁࡢ᭷↓ࠊࢽ࣡ࢺࣜࡢ⬻ࡸ B-⣽⬊࠿
ࡵࡽࢀࡓࠋ
ࡽศ㞳⢭〇ࡋࡓ CD24 ࡢ⢾㙐ᵓ㐀ࢆ᫂ࡽ࠿࡟ࡍࡿࠋࡑࡢ
ᚓࡽࢀࡓ⤖ᯝ࠿ࡽࠊNGF ่⃭࡟ࡼࡿ PC12 ⣽⬊ࡢࢽࣗ
➨୍࡜ࡋ࡚ࠊࢽ࣡ࢺࣜ CD24 ࡟ᑐࡍࡿᢠయࢆ㑇ఏᏊࢹ࣮
࣮ࣟࣥ࡬ࡢศ໬ࡢ㐣⛬࡛ࠊఱࡽ࠿ࡢᙳ㡪࡟ࡼࡗ࡚⣽⬊⭷
ࢱ࣮࣮࣋ࢫ࠿ࡽ CD24 㑇ఏᏊࢆ᥎ᐃࡋࠊࡑࡢ࢔࣑ࣀ㓟㓄
⾲㠃ࡢ CD24 ࡢⓎ⌧ࡀᢚไࡉࢀࠊࡑࡢ⤖ᯝ⭷⾲㠃࡟Ⓨ⌧
ิࢆ฼⏝ࡋ࡚ᢠయࡢసᡂࢆヨࡳࡓࠋ⌧ᅾࠊࡑࡢᢠయࢆ⏝
ࡉࢀࡿ࣏ࣜࣛࢡࢺࢧ࣑ࣥ㙐ࡀῶᑡࡍࡿࡇ࡜ࠋࡑࡋ࡚ࠊ⚄
࠸ࠊࣇ࢓ࣈࣜ࢟࢘ࢫᄞ࡟࠾ࡅࡿ CD24 㝧ᛶ⣽⬊ࢆ᳨⣴ࡋ
⤒✺㉳ࢆ▷᫬㛫࡛ᙧᡂࡍࡿኚ␗ᰴࡢ PC12D ⣽⬊࡛ࡣ
ࡓ࡜ࡇࢁࠊ㝧ᛶ⣽⬊ࢆほᐹࡍࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡋ࠿ࡋ࡞
NGF ᮍ่⃭࡛࠶ࡗ࡚ࡶࠊCD24 Ⓨ⌧㔞ࡀᢚไࡉࢀ࡚࠸ࡓ
ࡀࡽࠊCD24 㝧ᛶ⣽⬊ࡢ๭ྜࡀ┦ᑐⓗ࡟పࡃࠊࣇ࢓ࣈࣜ
࢟࢘ࢫᄞ࠿ࡽࡢ⢭〇ࡀᅔ㞴࡛࠶ࡗࡓࠋࡑࡇ࡛ࠊCD24 ࡢ
effect on PC12D cells. The isolated PL-GPs were analyzed by
Ⓨ⌧ࢆ☜ㄆࡋࡓࢽ࣡ࢺࣜⓑ⾑⑓⏤᮶ࡢᰴ⣽⬊࡛࠶ࡿ
SDS-PAGE and fluorography as well as the susceptibility to
DT-40 ࠿ࡽ CD24 ࡢ⢭〇ࢆヨࡳ࡚࠸ࡿࠋ⌧ᅾࡲ࡛ࡢ࡜ࡇ
endo-E-galactosidase. The amino acid sequence analysis of
ࢁࠊࢽ࣡ࢺࣜ CD24 ࡣࠊ࣐࢘ࢫࠊࣛࢵࢺ CD24 ࡜ྠᵝ࡟
62kDa PL-GP quite resembled that of rat CD24.
GPI ࢔࣮ࣥ࢝ࢆࡶࡘ⭷ࢱࣥࣃࢡ㉁࡛࠶ࡿࡇ࡜ࡀศ࠿ࡗࡓ
CD24 is a GPI-glycoprotein that is anchored to the
ࡀࠊ࣐࢘ࢫࠊࣛࢵࢺ CD24 ࡢศ㞳ࡢሙྜ࡜␗࡞ࡾࠊ᭷ᶵ
surface of cell membrane. To characterize carbohydrate
⁐፹࡟୙⁐࡛࠶ࡗࡓࠋ⢭〇ࡢ⛬ᗘࡣ୙࡛᫂࠶ࡿࡀࠊศ㞳
chains on 62kDa PL-GP (i.e. CD24), the nitrocellulose based
ࡋࡓ CD24 ࢆ౑⏝ࡋ࡚ࠊ⢾㙐࣐࢖ࢡࣟ࢔ࣞ࢖ࡢᢏ⾡ࢆ⏝
microarray system on which partially purified CD24 was
࠸࡚ࠊࣞࢡࢳࣥ MAA ࡜ SNA ࡟ࡼࡿ⤖ྜࢩࢢࢼࣝࢆ᥈ࡾࠊ
immobilized, were applied. This assay revealed that CD24
ࢩ࢔ࣝ㓟ṧᇶࡢ⤖ྜᵝᘧࢆ᥈⣴ࡋ࡚࠸ࡿࠋ
had not only poly-N-acetyllactosamine chains, but also the
poly-N-acetyllactosamine chains were terminated with
㸰㸬ᮏᖺᗘࡢ◊✲ᡂᯝ
O-blood type fucose residues, but not Lewis x and/or sialyl
1㸧CD24 ࡣ GPI ࢔࣮ࣥ࢝ᆺ⢾ࢱࣥࣃࢡ㉁࡛࠶ࡾࠊ≀⌮
Lewis x structures, for example. This microarray assays also
ⓗ࡞ᛶ≧ࡀ⢾⬡㉁ࡢࡑࢀ࡜㢮ఝࡍࡿࡇ࡜࠿ࡽࠊ᭷ᶵ⁐፹
suggested that the reason for the less content and having
ࢆ⏝࠸ࡓ⢭〇᪉ἲࢆ⏝࠸ࡿࡇ࡜࡛ຠ⋡ࡼࡃศ㞳࡛ࡁࡿࡇ
shorter poly-N-acetyllactosamine chains in PC12D cells
࡜ࢆ᫂ࡽ࠿࡜ࡋࡓࠋࡲࡓࠊࡇࡢᛶ㉁࠿ࡽࠊCD24 ࡣ⢾㙐
might be originated in less expression of CD24 gene in
࣐࢖ࢡࣟ࢔ࣞ࢖ἲ࡟┤᥋ᛂ⏝࡛ࡁࡓࠋ⢾㙐࣐࢖ࢡࣟ࢔ࣞ
addition to the less GnT-i activity.
࢖ࡢ⤖ᯝ࠿ࡽ PC12 ⣽⬊⏤᮶ࡢ CD24 ࡣࠊ࣏ࣜࣛࢡࢺࢧ
To explore the role of CD24 in an infection of A-type
࣑ࣥ⢾㙐௨እ࡟ࠊǂ2,3 ⤖ྜࡸ ǂ2,6 ⤖ྜࡋࡓࢩ࢔ࣝ㓟ࠊ
influenza virus, anti-serum against chicken CD24 was
fucose ྵ᭷⢾㙐࡞࡝ࢆྵࡴከᵝᛶ࡟ᐩࡴศᏊ࡛࠶ࡿࡇࡀ
constructed using some polypeptides that were different from
᫂ࡽ࠿࡟࡞ࡗࡓࠋ⯆࿡῝࠸ࡇ࡜࡟ࠊCD24 ࡣ⏤᮶ࡍࡿ⤌
amino acid sequence from those of mouse, rat CD24s.
⧊࡟ࡼࡗ࡚࣏ࣜࣛࢡࢺࢧ࣑ࣥ⢾ࡢࡳ࡞ࡽࡎ⢾㙐ࡢᵓᡂࢆ
anti-serum revealed the chick CD24, which was isolated from
␗࡟ࡋ࡚࠸࡚࠸ࡓࠋ2㸧CD24 ศᏊ࡟⤖ྜࡋ࡚࠸ࡿ࣏ࣜࣛ
DT-40 cells, to be a membrane glycoprotein with GPI-anchor.㻌
ࢡࢺࢧ࣑ࣥ㙐ࡣ N-ࢢࣜࢥࢩࢻᆺ⢾㙐࡟⤖ྜࡋ࡚࠸ࡿࡇ
Recently I could develop the efficient method to conjugate
࡜ࠋ3)ᐇ㦂࡟⏝࠸ࡓᢠ CD24 ࣔࣀࢡ࣮ࣟࢼࣝᢠయࡢᢠཎ
oligosaccharides with AlexaFluor 350.
Ỵᐃᇶࡣࠊࣛࢵࢺ࡜࣐࢘ࢫࡢ CD24 ࡢ࢔࣑ࣀ㓟㓄ิࡢ㐪
࠸࠿ࡽࠊN-ᮎ➃ 11㹼13 ␒┠ࡢ Asn-Gln-㸦N-glycan
bearing㸧Asn ࡢ㡿ᇦ࡜᥎ᐃࡉࢀ࡚࠸ࡓࡀࠊ13 ␒┠ࡢ Asn
㸲㸬ㄽᩥ
࡟ࣇࢥ࣮ࢫࡢ⤖ྜࡋࡓ࢟ࢺࣅ࣮࢜ࢫᵓ㐀ࡶྵࡲࢀࡿࡇ࡜
࡞ࡋ
ࡀศ࠿ࡗࡓࠋ4) ࢽ࣡ࢺࣜⓑ⾑⑓⏤᮶ࡢᰴ⣽⬊࡛࠶ࡿ
DT-40 ࠿ࡽ CD24 ࡢ⢭〇࡛ࡁࡓࠋࢽ࣡ࢺࣜ CD24 ࡣࠊ࣐
࢘ࢫࠊࣛࢵࢺ CD24 ࡜ྠᵝ࡟ GPI ࢔࣮ࣥ࢝ࢆࡶࡘ⭷ࢱࣥ
䠑Ꮫ఍Ⓨ⾲
ࣃࢡ㉁࡛࠶ࡿࡇ࡜ࡀศ࠿ࡗࡓࠋ5) ⢾㙐⤖ྜࡢ≉␗ᛶࡢ᥈
࡞ࡋ
⣴ࢆ┠ⓗ࡜ࡋ࡚ࠊ⢾㙐ࡢ㑏ඖᮎ➃࡟⺯ගヨ⸆ AlexaFluor
ࢆຠ⋡ࡼࡃ⤖ྜࡉࡏࡿ᪉ἲࢆぢฟࡋࡓࠋ
䠒㸬䛭䛾௚≉グ஦㡯
㸱㸬Research projects and annual reports
To explore the biological role of carbohydrate chains
in the process of nerve cell differentiation, I have carried out
characterization of the carbohydrate structure of glycoproteins
by comparing conventional PC12 cells with variant cells
(PC12D). Previously we showed that the length and content
of poly-N-acetyllactosamine chains obtained from the
membrane fraction differed significantly between PC12 and
PC12D, and also that NGF stimulation decreased the content
of poly-N-acetyllactosamine chains of PC12 cells, but had no
࡞ࡋ
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-*Research projects and annual reports
In the laboratory of Developmental Systems, the molecular
biological, cell biological and histological aspects of
organogenesis are being studied. The main targets of the study
are digestive organs, heart and gonad of the chicken and
Xenopus embryos.
(1) Smooth muscle layers of the digestive organs
Digestive organs in the vertebrates have specifically arranged
smooth muscle layers important for the transport of food
Ć !.5 ˆ…–ªÊȝȪğå & fĘĈ´JsiÍƑaȏPvƬf
through the gut. We analyzed the effects of environmental
ĹņĹŇơįb ' fĦĈBƬfȬÚLȏPvȗįfċȽŬÈagA«
factors on the differentiation of muscle layers.
®ŠĒǛǫfȶƼeȓGbPxe ' fĸGˆ…–ªLŶàRwvƯ
ìB& zō¶T[ƬagAƬfȬÚLȪğRwvbbqeA' f‰¢‘•ƙfˆ…–ªL«®ŠĒǛǫfČĴÖeȓGȟáeŶàRw
vƯUuBÍƑaƥƝRX[ȸȟagAƬLĒÖjbƺàTA' ˆ
(2) Localization of stem cells in the developing digestive
organs
To analyze the derivation and localization of stem cells in the
…–ªfţƮdĦĈgǹtwdGB
intestine during the development we studied the expression of
stem cell-specific markers, Lgr5, Sscl2 and Flm4 genes,
ɃɋɄƬfnjǢfȷĊêeȨVvƲƹ
during the intestinal development.
njǢîČaFvƬǜKtgAÙðĠdžǜr—¦°¬®
(3) Degeneration of right ovary in female chick embryo
zq_ƴLjłnjǢbYHadGnjǢǨDŽ³ƧzƝUvB
Avian ovary provides an interesting example of left-right
PfsHdƬǜfȷĊƘơƦáêgAûąfLJǑKtf
asymmetric development of organs. We analyzed the
ȄĤeÑĘT`ȏPvLAȄĤÏƟf´ƎadžǜǤļƦ
occurence of apoptosis during the development of ovary.
ețýƆĜeg[tNȞÊė˜‘•­°„eȨVvŅč
(4) Heart
gAƚĈfbPxŸp`ȫtw`GvBňCgA—­•
An important origin of coronary vessels in the heart, which
©fºĜƴLjłnjǢeƘơƦeƥƚVv _fȐÞăė
supply oxygen and nutrients to the entire myocardium, is an
ȞÊė.<69<"/<!<eƭƩTAYwZw
extracardiac rudiment called the proepicardium (PE). We
z /45;5 €«„•¬¢«°ˆ§®ƈzƟG`AºĜǨDŽ
studied tissue interactions that control fusion of the PE to the
³ƧeĸãƦeƥƚRX[BljŲA.< LǨDŽ³Ƨf
heart and molecular basis of these interactions. We also
ƥƝțýzƴLjłnjǢjbđIvg[tMzq_PbL
established techniques and molecular tools necessary to study
yK^[BPfțýȐŖgAöźfg[tMLŠečú
roles of soluble signaling molecules in coronary vessel
Rw`Gv "5<8.//+9'2fƥƚ³ŢzË
formation in the maturing heart.
^`JuA.< LA´Ǝf "5< bbqeAƬǜf›
(5) Eye morphogenesis
A cup-like morphology of the eye is a feature shared by
(4) Heart
most vertebrate species. This basic structure is generated
The epicardium and coronary vessels of the heart originate
through coordinated invagination of the optic vesicle and the
from an extracardiac rudiment called the proepicardium (PE).
lens ectoderm. We explored molecular and cellular basis of
Although the fusion of the PE to the heart is critical for
this morphogenetic event, using two avian models that exhibit
coronary vessel formation, its mechanisms remain unclear.
The PE always fuses to the atrioventricular junction (AVJ) of
failed invagination of the eye.
the heart, but not to the sinoatrium (SA) despite its proximity
(5) Patterning of the retinal primordium
During eye development the multipotential primordium of
to the PE. We therefore hypothesized that a short-range
the retina, the optic vesicle, is patterned into the neural retina
paracrine signal(s) from the AVJ triggers the fusion of the PE
and the retinal pigmented epithelium. Using in ovo
to this specific region of the heart. To test this hypothesis, we
electroporation, we analyzed functions of transcription factor
carried out in vivo implantation assay. An AVJ segment
isolated from a donor quail embryo was implanted into a chick
genes implicated in this patterning event.
host carefully, so that the host-derived PE maintains a contact
with the outer surface of implanted AVJ. Our histological
analysis demonstrated that the fusion of the PE to the
Results
implanted heart segment occurs within two hours and that this
fusion occurs preferentially to the AVJ (86%), rather than the
(1) Smooth muscle layers of the digestive organs
We analyzed the effect of the epithelium on the arrangements
SA (17%), providing evidence that AVJ and SA differ in
of smooth muscle layers by implanting mesodermal fragments
capability to induce (or permit) the PE fusion. To gain insights
into
When
into molecular basis of this regional difference, we carried out
presumptive stomach mesoderm was transplanted into
microarray analysis and in situ hybridization screening of
presumptive intestinal area, mesoderm differentiated muscle
candidate genes, and identified EphB3, which encodes a
layers not identical to those of stomach or intestine.
membrane-bound tyrosine kinase receptor, and Vcam1, which
Presumptive intestinal mesoderm formed muscle layers very
encodes a cell adhesion molecule, as genes expressed
similar to those of stomach. Thus the developmental fate of
preferentially in the AVJ. Using an improved protocol of in
the mesoderm is thought to be affected by the environmental
ovo lipofection, we are currently testing a potential role of
factors.
EphB3 in controlling the site of the PE fusion within the heart.
heterologous
presumptive
digestive
areas.
(2) Localization of stem cells in the developing digestive
organs
Major branches of coronary arteries show a stereotype
distribution within the heart. Understanding mechanisms
Last year we cloned chicken Lgr5 and Hairy1 genes and
underlying formation of this pattern will provide a foundation
revealed that Lgr5-positive cells first appeared on day 15 of
for rational therapeutics of coronary disorders, including
incubation at the base of the villi. This year we further
ischemic cardiac disease. Coronary vessels develop via
investigated the expression of Ascl2 and Flm4 genes that are
multiple steps, including induction and growth of the PE, the
expressed in adult stem cells. These genes are expressed rather
fusion of the PE to the heart, the epicardial coverage of the
widely in the lower half of the villi during the development,
heart
and become restricted to the crypt after hatch. Thus the
epicardial cells. To gain insights into key steps of coronary
expression of these genes is not specific to the stem cells
vessel formation, we examined development of Xenopus heart,
expressing Lgr5 gene, at least in the course of development.
which lacks coronary vessels. Expression of Tbx18 and
(3) Degeneration of right ovary in female chick embryo
Wilms' tumor-1 (Wt1), markers for the PE and epicardium,
and
epithelial-to-mesenchymal
transformation
of
To assess whether apoptosis is responsible for the
was detectable in or around the heart at stages when the PE
degeneration of right ovary in chick embryo, we detected
develops and fuses to the heart. However, we obtained no
apoptosis by TUNEL method from day 5 to 20 of embryonic
clear evidence for the presence of subepicardial connective
development. However, apoptosis was very rare and there was
tissue even in the adult heart, suggesting that reduced
no difference in its occurrence between left and right ovaries.
epicardial EMT correlates with lack of coronary vessels in the
Therefore, we concluded that apoptosis is not the direct cause
amphibian heart.
of degeneration of right ovary.
The above information led us to hypothesize that distribution
pattern of coronary vessels in amniote hearts is affected by the
.*&"
epicardial EMT. We have previously shown that soluble
signaling molecules, BMP2, FGF2, PDGF-BB, VEGF,
ÛūȋȲɌœ•zƛǼVv[pfƝƗęǵǪŊ
TGF-ß1, TGF-ß2, promote migration of cultured PE-derived
ÛūȋȲɌ‰°ƝƗęɃ"9'77;+78"9'77ǬɄ
ů¾êęö¿
cells (Ishii et al., 2010). To test potential roles of these factors
in promoting coronary vessels formation in vivo, we generated
transposon-based expression vectors.
/*#
(5) Eye morphogenesis
The eye in vertebrates has a cup-like retina and a vesicular
ÛūȋȲƏêāěfƥƝŽŹƛêęƲƹŋƥƝɍÝ
lens. This basic morphology is generated through coordinated
ƝƵęǍõƲƹ‹®° ƥƝƝƗę©‚«®•ȉĶƴʼn
ĬɃŏĻȉƔɄ
invagination of the optic vesicle and lens ectoderm. We found
that the head of chick embryos isolated at embryonic day 2
ÛūȋȲéƗfĹÏufȈšŪéƗęÉȓƢŘȟȉ
ƔɾȠƞŷĔęoViySȾɃŏĻȉƔɄ
and cultured in vitro generates invaginating eyes but fails to
do so if cultured at a low temperature (29-30@) or in the
8.//&:0/3595&'8:-/"<67+88/545,
presence of a Rho-signaling inhibitor Y-27632. Although this
,'3/2=-+4+8/483559.3:8)2+5,9.++3(7=54/)
abnormality was not associated with obvious changes in cell
)./)1+4*/-+89/;+57-'48
9.44++9/4-,57'6"5)
+;+256/52'98:+
proliferation, cell death and expression of developmental
genes, cell polarity regulators, Par3 and aPKC, and
Ʊ½ƊȲAǩƠǦAǭŪǘŃAÛūȋȲɌ—­•©ǛƏêǀİ
cell-adhesion related proteins, N-cadherin and ß-catenin,
ƓƿLJǑeJOv ȞÊėfƥƚšÁƝƗęÉƽ
exhibited abnormal distributions along the apicobasal axis of
ĂÐÉAů¾A
the lens ectoderm. Interestingly, such abnormality was not
Ʊ½ƊȲAǻƠƋİAÛūȋȲɅ²ĨȯɌŀǣfƥƝȜƷeJ
OvßéǞIJdžǜfșÚŽŹšÁƝƗęÉƽ ĂÐÉAÄ
seen in the optic vesicle. The data highlight the significance of
òA
the lens ectoderm in generating cup-like eye as a whole.
ÛūȋȲAǩƠǦAƱ½ƊȲɌ—­•©ǛfƏêāěƘơƦd
(6) Patterning of the retinal primordium
İƓƿħĹŇšÁƝƗęÉƽ ĂÐÉAÄòA
In vertebrates the retina develops from a part of the forebrain,
the optic vesicle. The distal portion of the optic vesicle (OV)
mainly gives rise to the light-sensitive neural retina (NR),
0*
%)
whereas its proximal part differentiates into the retinal
pigmented epithelium (RPE). While it is well-established that
Ēȟȍȣ
the patterning of the OV into NR and RPE domains depends
ƵęƲƹǴèȣ¯ČƨƲƹ on paracrine signals from the surrounding tissues, such as the
ȆȺ÷ßéǞ¯ŀĒǢäȿdžǜféņbYfãĿ
lens and cranial mesenchyme, little is known about the gene
ƲƹÅdzǗƱ½ƊȲAïľıĵ ı
regulatory
networks
underlying
this
patterning
event.
Transcription factor genes, Chx10, Optx2, Six3, Rx1, are all
ưȌƞżƾ dT
expressed in the presumptive NR but not in the RPE. We
misexpressed these genes in the presumptive RPE ectopically,
ęĒƍé
using in ovo electroporation in combination with a
ÛūȋȲɌƌǷɁƾęųŻŗŒŷ
transposon-mediated gene transfer, and identified Chx10 as a
ÛūȋȲAƱ½ƊȲDɁųƝƗŚǙþƲÔÉƥƝƝƗę©‚
gene capable of inhibiting RPE pigmentation. This inhibition
was associated with ectopic NR-like differentiation and
ectopic expression of a neural stem cell marker Sox2. Our data
«®•ȉĶEȉĮAƴʼnĬA
ÛūȋȲɌšŪéƗęÉȓƢŘȟȉƔÉDéƗfĹÏufȈz
bNE°ƒ–}‡°
suggest that Chx10, as well as its downstream gene Sox2, is an
ÛūȋȲšÁƝƗęÉIJ»
important component of a gene regulatory network that
ÛūȋȲɌšŪƥƝƝƗęÉŽȨȂǎȳĖþ
regulate OV cell fate in a cell autonomous manner.
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anti-parallel coiled coil structure without the globular-loop
part. Here we report that FliJ of Salmonella enterica serovar
Typhimurium shows a rotor like function in Thermus
thermophilus A3B3 based on both biochemical and structural
analysis. Single molecular analysis indicates that an
anti-parallel coiled-coil structure protein (FliJ structure
protein) functions as a rotor in A3B3. A rotary ATPase
possessing an F1-γ-like protein generated by fusion of the D
and F subunits of V1 rotates, suggesting F(1-γ) could be the
result of a fusion of the genes encoding two separate rotor
subunits. Together with sequence comparison among the
globular part proteins, the data strongly suggest that the rotor
domains of the rotary ATPases and the flagellar export
apparatus share a common evolutionary origin.
ÖT_H\YaƒJpsrC
! aǣǎ»ŭ
3. ATP sensing system in whole nematode
ƍƝeëþc¼ŭVrǣǎÌcoqBƍƝǨ¿ºGY
Adenosine 5′-triphosphate (ATP) is the major energy currency
qe! ǓMŝĆVrRaMBÀţuL\YC²eǣǎ
of all living organisms. Despite its important functions, the
Ì`mßʼne! ŝĆMƼRrRavűƧTYCjYB
spatiotemporal dynamics of ATP levels inside living
Ɔƕ`mǣǎÌcoq! ǓMõďcŝĆVrRaMu
multicellular organisms is unclear. In this study, we modified
L\YCŻƈƆƕÄe! šđv¨QrRa`ǣǎÑŃ
the genetically encoded Förster resonance energy transfer
MűĮSsrÝƖĞMŹåSsYC
(FRET)-based ATP biosensor ATeam to optimize its affinity
at low temperatures. This new biosensor, AT1.03NL, detected
Ǫ ǧResearch projects and annual reports
1. Molecular basis of ADP-inhibition of V type
ATPase/synthase.
Reduction of ATP hydrolysis activity of V type
ATPase/synthase (VoV1) as a result of ADP-inhibition occurs
as part of the normal mechanism of VoV1 of Thermus
thermophilus, but not VoV1 of Enterococcus hirae or
eukaryotes. To investigate the molecular basis for this
difference, domain swapped chimeric V1 consisting of both T.
thermophilus and E. hirae enzymes were generated and their
function analyzed. The data showed that the interaction
between the nucleotide binding and C terminal domains of the
catalytic A subunit from E. hirae V1 is central to increasing
binding affinity of the chimeric V1 for phosphate, resulting in
reduction of the ADP-inhibition. These findings together
with a comparison of the crystal structures of T. thermophilus
V1 with E. hirae V1 strongly suggest that the A subunit adopts
a different conformation in T. thermophilus V1 from that in E.
hirae V1. This key difference results in ADP inhibition of T.
thermophilus V1 by abolishing the binding affinity for
phosphate during ATP hydrolysis.
ATP changes inside Caenorhabditis elegans cells more
sensitively than the original biosensor did, at 25 °C. By
expressing
AT1.03NL
in
Caenorhabditis
elegans,
we
succeeded in imaging the in vivo ATP dynamics of these
model animals at single-cell resolution.that ATeam is
available for detection of ATP levels change in nematode
cells.
1.($"* Corresponding author
1. Tani K., Arthur C., Tamakoshi M., Yokoyama K., Mitsuoka
K., Fujiyoshi Y., *Gerle C., Visualization of Two distinct
states of disassembly in the bacterial V-ATPase from
Thermus
thermophilus.
Microscopy.
Vol.
62(4)
pp467-474
2. Kishikawa J., Ibuki T., Nakamura S., Nakanishi A.,
Minamino T., Miyata T., Namba K., Konno H., Ueno H.,
*Imada K., *Yokoyama K “Common evolutionary origin
for the rotor domain of rotary ATPases and Flagellar
2. Common evolutionary origin for the rotor domain of rotary
ATPases and flagellar protein export apparatus.
The V1- and F1- rotary ATPases contain a rotor that rotates
against a catalytic A3B3 or α3β3 stator. The rotor F(1-γ) or
V1-DF is composed of both anti-parallel coiled coil and
globular-loop parts. The bacterial flagellar type III export
apparatus contains a V1/F1-like ATPase ring structure
composed of FliI6 homo-hexamer and FliJ which adopts an
protein export apparatus.” PLoS One Vol. 8(5) e64695
3. Tsuyama T., Kishikawa J., Han Y.W., Harada Y.,
Tsubouchi A., Noji H., Kakizuka A., Yokoyama K.,
Uemura T., *Imamura H.@In vivo fluorescent ATP
imaging of Drosophila melanogaster and Caenorhabditis
**9.3,4+9-*.45->8.(&1 4(.*9>4+&5&3>494
elegans by using a genetically encoded fluorescent ATP
&5&3
biosensor optimized for low tempaeratures.” Anal. Chem.
Vol. 85(16) pp7889-7896
&0&3.8-. .8-.0&<& %404>&2& .3).3,
4. Kishikawa J., Nakanishi A., Furuike S., Tamakoshi M.,
.39*7+&(*'*9<**3749478:':3.98<.9-14<'.3).3,
*Yokoyama K. “Molecular basis of ADP-inhibition of V
&++.3.9>.3#4#!-*9-33:&1**9.3,4+9-*
type ATPase/synthase.” J. Biol. Chem. Vol. 289(1)
.45->8.(&1
4(.*9> 4+ &5&3 >494 &5&3
pp403-412
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ᩍᤵ ྜྷ⏣ ㈼ྑ
Prof. Masasuke Yoshida, Ph.D
ࢱࣥࣃࢡ㉁ᶵ⬟◊✲ᐊ ຓᩍ ඖᓥ ྐᑜ
Lab. Protein Function
Assit. Prof. Fumihiro Motojima, Ph.D
㸯㸬◊✲ᴫせ
䛿䚸୍ᗘ✵Ὕෆ䛻㛢䛨㎸䜑䜙䜜䛯ኚᛶ䝍䞁䝟䜽㉁䛾䛒䜛๭ྜ
㻌
䛜⥅⥆ⓗ䛻✵Ὕእ䜈₃䜜ฟ䛧䛶䛟䜛䛣䛸䜢Ⓨぢ䛧䛯䚹⌧ᅾ䛾
ᮏ◊✲ᐊ䛷䛿䛂ศᏊ䝅䝱䝨䝻䞁䛃䛸䛂㻭㼀㻼 ྜᡂ㓝⣲䛃䛻䛴䛔䛶
䝅䝱䝨䝻䝙䞁䛾స⏝ᶵᵓ䛾ᩍ⛉᭩ⓗ䛺䝰䝕䝹䛷䛿ኚᛶ䝍䞁
◊✲䛧䛶䛔䜛䚹㻌
䝟䜽㉁䛿᏶඲䛻✵Ὕෆ䛻㛢䛨㎸䜑䜙䜜䛶䛔䜛䚹䛧䛛䛧䚸✵Ὕ
ෆ䝣䜷䞊䝹䝕䜱䞁䜾䛾୰㛫≧ែ䛷䛿䚸✵Ὕෆ䛾ኚᛶ䝍䞁䝟䜽
ศᏊࢩࣕ࣌ࣟࣥ
㉁䛿䛭䛾䝫䝸䝨䝥䝏䝗䛾୍㒊䛜✵Ὕ䛾እ䜈䛿䜏䛰䛧䛶䛔䜛䜙
⣽⬊ࡢ୰ࡢಶࠎࡢࢱࣥࣃࢡ㉁ࡣࡑࢀࡒࢀಶᛶⓗ࡛࠶ࡾࠊ
䛧䛔䚹ᐇ㝿䚸䛣䛾୰㛫≧ែ䛾Ꮡᅾ䛿䚸⁐ᾮ䛻ຍ䛘䛯ᢠᇶ㉁䝍
ࡑࡢㄌ⏕࠿ࡽᾘ⁛ࡲ࡛ከᵝ࡞㐠࿨ࢆࡓ࡝ࡿ࡟ࡶ࠿࠿ࢃࡽ
䞁䝟䜽㉁ᢠయ䛜✵Ὕෆ䛻ධ䛳䛶䛔䜛ኚᛶ䝍䞁䝟䜽㉁䛻⤖ྜ䛧
ࡎࠊ⣽⬊ࡣ⤫୍ⓗ࡞ᶵ⬟ࢆ⥔ᣢࡋ࡚࠸ࡿࠋࡉࡽ࡟ࠊ⎔ቃ
䛶䚸✵Ὕෆ䛾䝣䜷䞊䝹䝕䜱䞁䜾䛾㐍⾜䜢೵Ṇ䛥䛫䜛䛣䛸䛷☜
ࡀኚ໬ࡍࢀࡤࡑࢀ࡟ᛂࡌ࡚ࢱࣥࣃࢡ㉁ࡢࠕ♫఍ࠖࢆ෌⦅
䛛䜑䜙䜜䛯䚹ኚᛶ䝍䞁䝟䜽㉁䛿✵Ὕෆ䛻䜟䛪䛛䛻㟢ฟ䛩䜛␯
ᡂ࡛ࡁࡿࠋࢱࣥࣃࢡ㉁ࡢಶᛶࡣ❧యᵓ㐀࡛つᐃࡉࢀ࡚࠸
Ỉᛶ䛾䝃䝤䝴䝙䝑䝖⏺㠃㏆ഐ䛾䝅䝇䝔䜲䞁䛸䝆䝇䝹䝣䜱䝗ᯫᶫ
ࡿࠋࡑࡋ࡚ࠊ❧యᵓ㐀ࡢ⛣ࡾኚࢃࡾࢆไᚚࡍࡿศᏊࢩࣕ
䜢ᙧᡂ䛧䚸ኚᛶ䝍䞁䝟䜽㉁䛿䛣䛾㡿ᇦ䛸␯Ỉᛶ┦஫స⏝䛧䛶
࣌ࣟࣥࡣࠊࢱࣥࣃࢡ㉁♫఍ࡢ⤫ᚚ࡟㔜せ࡞ᙺ๭ࢆᯝࡓࡋ
䛔䜛䛸⪃䛘䜙䜜䛯䚹䜎䛯䚸␯Ỉᛶ䜢ῶᑡ䛥䛫䛯 㻳㼞㼛㻱㻸 ኚ␗య
࡚࠸ࡿࠋᮏ◊✲ศ㔝࡛ࡣศᏊࢩࣕ࣌ࣟࣥࡢస⏝ᶵᵓ࡟ࡘ
䛿䝣䜷䞊䝹䝕䜱䞁䜾䛜㐜䛟䛺䜚䚸␯Ỉᛶ┦஫స⏝䛜䝣䜷䞊䝹
࠸࡚◊✲ࡋ࡚࠸ࡿࠋ
䝕䜱䞁䜾䛾ಁ㐍䛻ാ䛟ྍ⬟ᛶ䛜♧၀䛥䜜䛯䚹ୖ䛾◊✲䛛䜙䚸
ᮏᙜ䛾✵Ὕෆ䝣䜷䞊䝹䝕䜱䞁䜾䜢ほᐹ䛩䜛䛻䛿䚸✵Ὕእ䛻₃
ATP ྜᡂ㓝⣲
䜜ฟ䛯䝫䝸䝨䝥䝏䝗䛾⮬Ⓨⓗ䝣䜷䞊䝹䝕䜱䞁䜾䜢ᕪ䛧ᘬ䛟ᚲ
ATP ࡣ඲⏕≀ࡢ࢚ࢿࣝࢠ࣮㏻㈌࡛࠶ࡾࠊATP ྜᡂ㓝⣲
せ䛜䛒䜛䛣䛸䜒♧䛥䜜䛯䚹౛䛘䜀䝬䝹䝖䞊䝇⤖ྜ䝍䞁䝟䜽㉁ኚ
ࡀ ATP ྜᡂࡢ኱㒊ศࢆㄳࡅ࠾ࡗ࡚࠸ࡿࠋATP ྜᡂ㓝⣲ࡣࠊ
␗య 㻰㻹㻹㻮㻼 䛿඲䛶✵Ὕෆ䛷䝣䜷䞊䝹䝕䜱䞁䜾䛩䜛䛸䛥䜜䛶
2 ࡘࡢᅇ㌿࣮ࣔࢱ࣮ࡢ」ྜࡋࡓࡶࡢ࡛࠶ࡿࠋࡘࡲࡾࠊATP
䛔䛯䛜䚸ᐇ㝿䛿 㻥㻜㻑䜒✵Ὕእ䛷䝣䜷䞊䝹䝕䜱䞁䜾䛧䛶䛔䛯䚹✵
ຍỈศゎ࡛㥑ືࡉࢀࡿ F1 ࣮ࣔࢱ࣮࡜ࠊࣉࣟࢺࣥ㸦ࡘࡲ
Ὕෆ㈇㟁Ⲵ䛻䜘䜛Ỉ࿴Ỉ䛾Ᏻᐃ໬䛜䝣䜷䞊䝹䝕䜱䞁䜾䜢ಁ
ࡾỈ⣲࢖࢜ࣥ㸧࡛㥑ືࡉࢀࡿ FO ࣮ࣔࢱ࣮࡛࠶ࡿࠋࡑࡋ
㐍䛩䜛䛸䛧䛯ㄝ䛿䛣䛾ㄗ䛳䛯ᐇ㦂⤖ᯝ䛻ᇶ䛵䛔䛶䛔䛶䛚䜚䚸
࡚୧⪅ࡣࠊඹ㏻ࡢࢩࣕࣇࢺ㸦ᅇ㌿㍈㸧࡛㐃⤖ࡉࢀ࡚࠸ࡿࠋ
ྰᐃ䛥䜜䛯䚹䜎䛯䚸㼏㼛㼚㼒㼕㼚㼑㼙㼑㼚㼠 䝰䝕䝹䜢⿬௜䛡䜛䛸䛥䜜䛯⣙
FO ࣮ࣔࢱ࣮ࡀࣉࣟࢺ࡛ࣥᅇ㌿ࡍࢀࡤࠊF1 ࣮ࣔࢱ࣮ࡣ㏫ᅇ
㻝㻜 ಸ䛾䝣䜷䞊䝹䝕䜱䞁䜾㏿ᗘୖ᪼䛿䚸䝍䞁䝟䜽㉁ኚᛶ䛻⏝䛔
㌿ࢆᙉ࠸ࡽࢀ࡚ࠊࡑࡢ⤖ᯝࠊATP ࡀྜᡂࡉࢀࡿࠋF1 ࣮ࣔ
䛯䜾䜰䝙䝆䞁ሷ㓟䛜⮬Ⓨⓗ䝣䜷䞊䝹䝕䜱䞁䜾䜢㐜䛟䛩䜛䛣䛸䛜
ࢱ࣮ࡢᅇ㌿ࡣ㢧ᚤ㙾࡛┤ど࡛ࡁࡿࡢ࡛ࠊ1 ศᏊほᐹ࡟ࡼ
ཎᅉ䛷䛒䜚䚸ᒀ⣲ኚᛶ䛾ሙྜ䚸㻞 ಸ⛬ᗘ䛧䛛ಁ㐍䛥䜜䛺䛔䛣䛸
ࡿᶵ⬟ゎᯒࡀ࡛ࡁࡿࠋࡲࡓࠊࡇࡢ࣮ࣔࢱ࣮࡟ࡣไᚚ⿦⨨
䜢ぢฟ䛧䛯䚹
ࡀᚲせ࡛࠶ࡿࠋᮏ◊✲ศ㔝࡛ࡣ ATP ྜᡂ㓝⣲ࡢᵓ㐀ࠊᶵ
ᵓࠊไᚚ࡟ࡘ࠸࡚◊✲ࢆᒎ㛤ࡋ࡚࠸ࡿࠋ
ATP ྜᡂ㓝⣲
㸯㸧ࣄࢺ F1 ࣮ࣔࢱ࣮ࡢᅇ㌿ゐ፹ᶵᵓ
㸰㸬ᮏᖺᗘࡢ◊✲ᡂᯝ
௒ࡲ࡛࡟⣽⳦ࡢ $73 ྜᡂ㓝⣲࠾ࡼࡧࡑࡢ㒊ศ」ྜయ࡛࠶
ࡿ F1 ࣮ࣔࢱ࣮ࡢᅇ㌿≉ᛶ࡟ࡘ࠸࡚ࡣࠊࡼࡃゎᯒࡉࢀ࡚ࡁ
ศᏊࢩࣕ࣌ࣟࣥ
ࡓࠋࡑࢀ࡟ࡼࡿ࡜ࠊATP ࡀ F1 ࡟⤖ྜࡍࡿ࡜ࠊ࣮ࣟࢱ࣮࡛
㸯㸧኱⭠⳦ GroEL ࡢస⏝ᶵᵓ
࠶ࡿ γ ࢧࣈࣘࢽࢵࢺࡣ 80°ᅇ㌿ࡍࡿࠋ80°ࡢ఩⨨࡛ࠊATP
䠴⥺⤖ᬗᵓ㐀䜔⏕໬Ꮫⓗᐇ㦂䛛䜙䚸䝅䝱䝨䝻䝙䞁
ຍỈศゎࡀ㉳ࡇࡾࠊࣜࣥ㓟ࡢゎ㞳ࡀ㉳ࡇࡾࠊ40°ᅇ㌿ࡋࠊ
䠄㻳㼞㼛㻱㻸㻛㻳㼞㼛㻱㻿䠅䛿ኚᛶ䝍䞁䝟䜽㉁䜢䛭䛾ぶỈᛶ✵Ὕ䛻㛢䛨
120°ࡢᅇ㌿࡜࡞ࡿࠋࡇࢀࡀ඲⏕≀࡟࡜ࡗ࡚ඹ㏻࡞ࡢ࠿ࠊ
㎸䜑䛶䝣䜷䞊䝹䝕䜱䞁䜾䜢᥼ຓ䛩䜛䛣䛸䛜᫂䜙䛛䛸䛺䛳䛶䛔䜛䚹
࣑ࢺࢥࣥࢻࣜ࢔ࡢ F1 ࣮ࣔࢱ࣮ࡢᅇ㌿ࢆゎᯒࡍࡿᚲせࡀ࠶
䛭䛧䛶䝅䝱䝨䝻䝙䞁䛿ኚᛶ䝍䞁䝟䜽㉁䜢✵Ὕෆ䛻㝸㞳䛩䜛䛣
ࡿࠋࡋ࠿ࡋࠊࡇࢀࡣࡇࡢ 15 ᖺ㛫ࠊୡ⏺ࡢㄡࡶ࡛ࡁ࡞࠿ࡗ
䛸䛷ኚᛶ䝍䞁䝟䜽㉁ྠኈ䛾⤖ྜ䛻䜘䜛୙ྍ㏫䛺จ㞟యᙧᡂ
ࡓࠋ௒ᅇࠊ⚾ࡓࡕࡣ 1 ศᏊほᐹ࡟ࡼࡗ࡚ࠊࣄࢺࡢ F1 ࣮ࣔ
䜢㜼ᐖ䛧䚸㛢䛨㎸䜑䜙䜜䛯ኚᛶ䝍䞁䝟䜽㉁䛿⮬⏤䛻䝣䜷䞊䝹
ࢱ࣮ࡢᅇ㌿ࢆぢࡿࡇ࡜ࡀ࡛ࡁࡓࠋࡑࡢ⤖ᯝࡣࠊ௨ୗࡢ㏻
䝕䜱䞁䜾䛩䜛䛸⪃䛘䜙䜜䛶䛝䛯㻔㻭㼚㼒㼕㼚㼟㼑㼚㻌㼏㼍㼓㼑 䝰䝕䝹㻕䚹⚾䛯䛱
ࡾࡔࡗࡓࠋATP ࡀ F1 ࡟⤖ྜࡍࡿ࡜ࠊγ ࢧࣈࣘࢽࢵࢺࡣ 65°
ᅇ㌿ࡍࡿࠋࡑࡋ࡚ඛ࡟ຍỈศゎࡉࢀ࡚ F1 ୖ࡟ṧࡗ࡚࠸ࡓ
acceleration was proposed based on experiments using GroEL
ࣜࣥ㓟ࡀゎ㞳ࡋ࡚ 65°࠿ࡽ 90°ࡲ࡛ᅇ㌿ࡍࡿࠋ90°ࡢ఩⨨
single-ring (SR) mutants SR1 and SRKKK2. We revisited
࡛ࠊATP ຍỈศゎࡀ㉳ࡇࡾࠊ30°ᅇ㌿ࡋࠊ120°ࡢᅇ㌿࡜࡞
these experiments and discovered several inconsistencies with
ࡿࠋࡇࡢࡼ࠺࡟ࠊ⣽⳦࡜࣑ࢺࢥࣥࢻࣜ࢔࡛ࡣࠊF1 ࡢ೵Ṇ
the previously reported conclusion. (i) SR1 was assumed to
ゅᗘࡀ㐪ࡗ࡚࠸ࡿࠋࡲࡓࠊ㜼ᐖᅉᏊ࡛࠶ࡿ IF1 ࡣࠊᅇ㌿
bind to GroES stably and to mediate single-round folding in
ࢆ 90°ࡢ఩⨨࡛೵Ṇࡉࡏࡿࡇ࡜ࡀࢃ࠿ࡗࡓࠋ
the cage. However, we show that SR1 repeats multiple
㸰㸧⣽⳦ F1 ࣮ࣔࢱ࣮ࡢ໬Ꮫ࣭ຊᏛඹᙺࡢ௙⤌ࡳ
turnovers of GroES release/binding coupled with ATP
⣽⬊ࡢ୰ࡢ࢚ࢿࣝࢠ࣮≧ែ㸦ATP ⃰ᗘࠊࣉࣟࢺࣥ⃰ᗘ໙
hydrolysis. (ii) Although the slow folding by SRKKK2 was
㓄ࠊ࡞࡝㸧ࡣ࠸ࢁ࠸ࢁኚࢃࡿࠋ࠸ࢁ࠸ࢁኚࢃࡗ࡚ࡶࠊ
attributed to mutations that neutralize negative charges on the
ATP ྜᡂ㓝⣲ࡣࠊATP ⃰ᗘяࣉࣟࢺࣥ⃰ᗘ໙㓄ࡢ࢚ࢿࣝ
cage wall, we found that the majority of substrate polypeptides
ࢠ࣮ኚ᥮ຠ⋡ࢆ࠸ࡘ࡛ࡶ 100㸣㏆࠸ຠ⋡࡛࠾ࡇ࡞࠺ࡇ࡜
escape from SRKKK2 and undergo spontaneous folding in the
ࡀồࡵࡽࢀ࡚࠸ࡿࡋࠊᐇ㝿࡟ࡑ࠺ࡋ࡚࠸ࡿࠋ࡝࠺ࡋ࡚ࡑ
bulk medium. (iii) It was proposed that an osmolyte,
ࢇ࡞ࡇ࡜ࡀྍ⬟࠿ࠋ⣽⳦ࡢ F1 ࡢ࣮ࣟࢱ࣮࡟☢Ẽᚤ⢏Ꮚࢆ
trimethylamine
௜╔ࡋࠊእ㒊☢ሙ࡟ࡼࡗ࡚ࡺࡗࡃࡾ࡜ᙉไⓗ࡟ᅇࡍ࡜ࠊ
folding by mimicking the effect of cage wall negative charges
ࡑࢀ࡟㏫ࡽࡗ࡚ᑡࡋ㐜ࢀ࡞ࡀࡽࠊ࠶ࡿ࠸ࡣᑡࡋඛ࡟ᅇ㌿
of WT GroEL and ordering the water structure to promote
N-oxide,
accelerated
SRKKK2-mediated
ࡍࡿࡢࡀほᐹࡉࢀࡿࠋࡇࢀࡣ F1 ࡢࢺࣝࢡ࡟ࡼࡿࡶࡢ࡛࠶
protein compaction. However, our results demonstrate that
ࡾࠊࡇࡢ᪉ἲ࡛ 360°ࡢࢺࣝࢡࡢ኱ࡁࡉࢆồࡵࡽࢀࡿࠋࡑ
in-cage folding by SRKKK2 is unaffected by trimethylamine
ࡢ⤖ᯝࠊATP ࡀᏑᅾࡍࡿ࡜ࠊࢺࣝࢡࡣࠊ0°ࠊ40°ࠊ80°࡛
N-oxide. (iv) Finally, although it was reported that SRKKK2
ࢪࣕࣥࣉࡋ࡚₞ῶࡍࡿࡢࡇࡂࡾࡢลࡢࡼ࠺࡞ࣃࢱ࣮ࣥࢆ
lost
120°ࡈ࡜࡟⧞ࡾ㏉ࡋ࡚࠸ࡓࠋATP ⃰ᗘࡀ㧗ࡅࢀࡤࠊ0°ࡢ
ribulose-1,5-bisphosphate carboxylase/oxygenase, we found
ࢪࣕࣥࣉࡢࢱ࢖࣑ࣥࢢࡀ 0°ࡼࡾࡶ᪩ࡲࡾࠊࡢࡇࡂࡾࡢล
that SRKKK2 retains this ability. Our results argue against the
ࡣ㧗ࡃ࡞ࡾࠊᅇ㌿ࡢ࢚ࢿࣝࢠ࣮ࡣ኱ࡁࡃ࡞ࡿࠋࡇࡢࡼ࠺
role of the negative charges on the cage wall of GroEL in
࡟ࡋ࡚ࠊ㧗࠸ ATP ⃰ᗘ㸦኱ࡁ࡞'GATP㸧ࡣࣟࢫ࡞ࡃᅇ㌿
substrate protein folding. Thus, in chaperonin studies, folding
ࡢᶵᲔⓗ࡞࢚ࢿࣝࢠ࣮࡟ኚ᥮ࡉࢀࡿࠋ
kinetics need to be examined thoroughly to determine the
㸱㸧ATP ྜᡂ㓝⣲ࡢ㜼ᐖᅉᏊ IF1 ࡢᙺ๭
fraction of the real in-cage folding.
the
ability
to
assist
the
folding
of
࣑ࢺࢥࣥࢻࣜ࢔ࡢ ATP ྜᡂ㓝⣲㸦࠾ࡼࡧ F1㸧ࡢ ATP ຍ
Ỉศゎάᛶࢆ㜼ᐖࡍࡿㄪ⠇ᅉᏊ࡜ࡋ࡚ IF1 ࡀ▱ࡽࢀ࡚࠸
ATP synthase
ࡿࠋIF1 ࡀ࡞࠸࡜ࠊ࣑ࢺࢥࣥࢻࣜ࢔ࡢࢡࣜࢫࢸᵓ㐀ࡀ࡛ࡁ
1) Rotary mechanism of human mitochondrial F1
࡟ࡃ࠸࡜࠿ࠊ࢔࣏ࢺ࣮ࢩࢫࡀ㉳ࡁࡸࡍ࠸ࠊ࡜࠿ሗ࿌ࡀ࠶
The rotary motor enzyme F1-ATPase (F1) is a catalytic
ࡿࠋ⚾ࡓࡕࡣ IF1 㑇ఏᏊࢆ᏶඲࡟Ḟᦆࡋࡓ࣐࢘ࢫࢆసᡂ
subcomplex of FoF1-ATP synthase that produces the majority
ࡋࡓࠋணᮇ࡟཯ࡋ࡚ࠊࡇࡢ࣐࢘ࢫࡣㄪ࡭ࡓ㝈ࡾ࡛ࡣࡲࡗ
of ATP in respiring cells. Chemo-mechanical coupling has
ࡓࡃ೺ᗣ࡛࠶ࡾࠊṇᖖ࡞࣐࢘ࢫ࡜༊ูࡀࡘ࠿࡞࠸ࠋIF1
been studied extensively for bacterial F1 but very little for
࡟௦ࢃࡿㄪ⠇ᅉᏊࡀᏑᅾࡍࡿࡢ࠿ࠊ࠶ࡿ࠸ࡣࠊATP ྜᡂ
mitochondrial F1. Here, we visualize and analyze ATP-driven
㓝⣲ࡣไᚚࡉࢀࡿᚲせࡀ࡞࠸ࡢ࠿ࠊ᳨ウࡀᚲせ࡞஦ែ࡜
rotation of human mitochondrial F1. A rotor-shaft J-subunit in
࡞ࡗࡓࠋ
the stator D3E3 ring rotates 120° per ATP accompanying three
catalytic steps; ATP binding to one E-subunit at 0°, Pi release
㸱㸬Research projects and annual reports
from another E-subunit at 65°, and ATP hydrolysis on the
third E-subunit at 90°. Rotation is often interrupted at 90° by
We are studying two independent projects; molecular
persistent ADP binding and is stalled at 65° by a specific
chaperones and ATP synthase.
inhibitor azide. These features are different from those of the
bacterial F1, in which all of the above events except ATP
Molecular chaperones
Chaperonin GroEL mediates the folding of protein
binding occur at 80°. A mitochondrial endogenous inhibitor
for FoF1-ATP synthase, IF1, blocks rotation at 90°.
encapsulated in a large cavity that, when sealed by GroES, is
2) Chemo-mechanical coupling of bacterial F1
referred to as the central cage. Recently, a critical role of
F1-ATPase (F1) is a motor enzyme, in which J subunit rotates
negative charge clusters on the cage wall in folding
120q per ATP in the D3E3 cylinder. During the operation, the
chemical energy of ATP hydrolysis ('GATP) is converted
interactions
~100% into the mechanical energy of rotation. However, the
between
the
bacterial
chaperonin
GroEL
and
unstructured proteins.. J Biosci Bioeng. 2013 Aug;116(2):160-4.
mechanism for such efficient conversion is yet unknown. Here
Nakamura J, Fujikawa M, Yoshida M. IF1, a natural inhibitor of
we show the profiles of torque as a function of the rotary angle
mitochondrial ATP synthase, is not essential for the normal growth
under various 'GATP conditions. The profiles show three
and breeding of mice. Biosci Rep. 2013 Sep 17;33(5).
jumps of torque at about 0q 40qand 80q in a 120q rotation
Sugawara K, Fujikawa M, Yoshida M. Screening of protein kinase
each followed by a gradual descent, indicating that F1
inhibitors and knockdown experiments identified four kinases that
generates torque by the transitions between three states. The
affect mitochondrial ATP synthesis activity. FEBS Lett. 2013 Nov
angular position of the transition makes a shift as the
29;587(23):3843-7.
concentrations of ATP, ADP and P i vary. These results not
Fujikawa M, Ohsakaya S, Sugawara K, Yoshida M. Population of
only suggest how F1 rotates but also explain how F1 varies
ATP synthase molecules in mitochondria is limited by available
torque reflecting change of environmental 'GATP, thus
6.8-kDa
providing a missing link between its rotation scheme and
Feb;19(2):153-60.
energetics.
proteolipid
protein
(MLQ).
Genes
Cells.
2014
Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H,
2) IF1 knock-out mice are as healthy as wild-type mice
Nakano A, Higo S, Yamazaki S, Matsuzaki T, Takafuji K, Asanuma
IF1 is an endogenous inhibitor protein of mitochondrial ATP
H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H,
synthase. It is evolutionarily conserved throughout all
Kitakaze M, Komuro I, Asano Y, Takashima S. Evaluation of
eukaryotes and it has been proposed to play crucial roles in
intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a
prevention of the wasteful reverse reaction of ATP synthase,
positive regulator of oxidative phosphorylation. Proc Natl Acad Sci
in the metabolic shift from oxidative phosphorylation to
U S A. 2014 Jan 7;111(1):273-8.
glycolysis, in the suppression of reactive oxygen species
Kang SJ, Todokoro Y, Yumen I, Shen B, Iwasaki I, Suzuki T, Miyagi
generation, in mitochondria morphology and in haem
A, Yoshida M, Fujiwara T, Akutsu H. Active-site structure of the
biosynthesis in mitochondria, which leads to anemia. Here, we
thermophilic foc-subunit ring in membranes elucidated by
report the phenotype of a mouse strain in which IF1 gene was
solid-state NMR. Biophys J. 2014 Jan 21;106(2):390-8
destroyed. Unexpectedly, individuals of this IF1-knockout
Morino1 M, Suzuki T, Ito M, Krulwich T. E. (2014) Purification and
mouse strain grew and bred without defect. The general
functional reconstitution of a seven-subunit Mrp-type Na+/H+
behaviors, blood test results and responses to starvation of the
antiporter,
J Bacteriol, 196(1), 28-35.
IF1-knockout mice were apparently normal. There were no
.
abnormalities in the tissue anatomy or the autophagy.
㸳㸬ⴭ᭩࠾ࡼࡧ⥲ㄝ࡞ࡋ
Mitochondria of the IF1-knockout mice were normal in
morphology, in the content of ATP synthase molecules and in
㸴㸬ᣍᚅㅮ₇ࠊࢩ࣏ࣥࢪ࣒࢘➼
ATP synthesis activity. Thus, IF1 is not an essential protein
for mice despite its ubiquitous presence in eukaryotes.
ྜྷ⏣㈼ྑ ⣽⬊࿧྾࡜ ATP ྜᡂ ⛉Ꮫᮍ᮶㤋 2013 ᖺ 5 ᭶ 16 ᪥
ྜྷ⏣㈼ྑ ⣽⬊࿧྾࡜ ATP ྜᡂ ᮾி኱Ꮫ་Ꮫ㒊 2013 ᖺ 10 ᭶
㸲㸬Ⓨ⾲ㄽᩥ
10 ᪥
Yoshida M.
Nojima T, Konno H, Kodera N, Seio K, Taguchi H, Yoshida M.
Nano-scale alignment of proteins on a flexible DNA backbone.
PLoS One. 2012;7(12):e52534. doi: 10.1371
Hara S, Nojima T, Seio K, Yoshida M, Hisabori T. DNA-maleimide:
an improved maleimide compound for electrophoresis-based
Mammalian ATP synthase; from single molecule to
body ࢻ࢖ࢶ Bochum.Univ. 2014. Jan. 10
Yoshida M. Motojima F. Renovation of chaperonin mechanism after
15 years; a tethering polypeptide in the "football" cage folds in-cage
or escapes out Bochum.Univ. 2014. Jan. 10
Yoshida M., Motojima F. “Football” with tethered polypeptide:
titration of reactive thiols in a specific protein. Biochim Biophys
Renovation of chaperonin mechanism
Protein folding, in and out
Acta. 2013 Apr;1830(4):3077-81
of Anfinsen’s closet
2014. 1.14
Nishida N, Yagi-Utsumi M, Motojima F, Yoshida M, Shimada I, Kato
K Nuclear magnetic resonance approaches for characterizing
ࢫ࢖ࢫ Arolla
㕥ᮌಇ἞ ⏕࿨ࡢ ATP ࢩࢫࢸ࣒ࢆసࡾฟࡍ FoF1-ATP ྜᡂ㓝⣲ࠊ
኱㜰኱Ꮫ ་Ꮫ㒊ㅮ₇఍ (኱㜰) ࠊ2014 ᖺ 1 ᭶ 23 ᪥
◊✲௦⾲⪅㸸ྜྷ⏣㈼ྑ 㸦+㸧
㸵㸬Ꮫ఍Ⓨ⾲
㸰㸬▱㈈ᶒ➼㸹
⛯⏣ⱥ୍㑻ࠊᮌୗ୍ᙪࠊྜྷ⏣㈼ྑ0LFURVWUXFWXUHRIWKHWRUTXH
JHQHUDWHGE\)$73DVH᪥ᮏ⏕≀≀⌮Ꮫ఍ᖺ఍
ி㒔
⸨ᕝㄔࠊⳢཎెዉᏊࠊྜྷ⏣㈼ྑࣄࢺ )R) ࡢ Gࢧࣈࣘࢽࢵࢺ
࡞ࡋ
㸱㸬Ꮫእάື㸸
ྜྷ⏣㈼ྑᮾி኱Ꮫ་Ꮫ㒊㠀ᖖ໅ㅮᖌ
ࣀࢵࢡࢲ࢘ࣥᰴࢆ⏝࠸ࡓ )R) ࢔ࢭࣥࣈࣜᶵᵓࡢゎᯒ᪥ᮏ⏕
ྜྷ⏣㈼ྑ-67&5(67ࠕࣛ࢖ࣇࢧ࢖࢚ࣥࢫࡢ㠉᪂ࢆࡵࡊࡋࡓ
య࢚ࢿࣝࢠ࣮◊✲఍➨ ᅇウㄽ఍࣭㟼ᒸ
ᵓ㐀⏕࿨⛉Ꮫ࡜ඛ➃ⓗᇶ┙ᢏ⾡ࠖ㡿ᇦ࢔ࢻࣂ࢖ࢨ࣮
ඖᓥྐᑜࠊඖᓥ㸦ᐑᓮ㸧ඃᏊࠊྜྷ⏣㈼ྑ. ࢩࣕ࣌ࣟࢽࣥࡀࢱࣥ
ࣃࢡ㉁ࣇ࢛࣮ࣝࢹ࢕ࣥࢢࢆ᥼ຓࡍࡿ௙⤌ࡳ. ᪥ᮏ⺮ⓑ㉁⛉Ꮫ
఍ࠊ2013. 6. 11-13ࠊ㫽ྲྀ
ඖᓥྐᑜ.ࢩࣕ࣌ࣟࢽࣥ᥼ຓࣇ࢛࣮ࣝࢹ࢕ࣥࢢ࡟࠾ࡅࡿࢱࣥࣃ
ࢡ㉁ࡢᦂࡽࡂᢚไࡢゎᯒ. ᅜ㝿㧗➼◊◊✲ࣉࣟࢪ࢙ࢡࢺ➨஧
ᅇ◊✲఍ࠊ2013. 8. 8-9. ி㒔
Kang S, Todokoro Y, Yumen I, Shen B, Iwasaki I, Suzuki T, Miyagi
A, Yoshida M, Fujiwara T, Akutsu HࠊThe Active-Site Structure of
Thermophilic FoF1-ATP Synthase c-Subunit Rings in Membranesࠊ
➨ 51 ᅇ᪥ᮏ⏕≀≀⌮Ꮫ఍ᖺ఍ࠊ2013 ᖺ 10 ᭶ࠊி㒔
Tasaki K, Kasuya Y, Soga N, Suzuki T, Yoshida M, Kazuhiko
Kinosita JrࠊQuantitative assay of ATP-driven proton-pump activity
of FoF1ࠊ➨ 51 ᅇ᪥ᮏ⏕≀≀⌮Ꮫ఍ᖺ఍ࠊ2013 ᖺ 10 ᭶ࠊி㒔
Suzuki T, Tanaka K, Wakabayashi C, Furuike S, Saita E, Kinosita K,
Yoshida M ࠊ Single molecule analyses of human F1-ATPase
revealed distinct rotation scheme of mitochondrial F1 motor.ࠊ➨ 51
ᅇ᪥ᮏ⏕≀≀⌮Ꮫ఍ᖺ఍ࠊ2013 ᖺ 10 ᭶ࠊி㒔
㕥ᮌಇ἞ࠊ⏣୰୍ᕭࠊⱝᯘ༓᫭ࠊྂụ ᬗࠊ⛯⏣ⱥ୍㑻ࠊᮌୗ୍
ᙪࠊྜྷ⏣㈼ྑࠊࣄࢺ F1-ATPase ࡢ୍ศᏊゎᯒࡀ᫂ࡽ࠿࡟ࡋࡓࠊ
ࣂࢡࢸࣜ࢔࡜ࡣ␗࡞ࡗࡓ࣑ࢺࢥࣥࢻࣜ࢔ F1 ࡢᅇ㌿ࢫ࣮࣒࢟ࠊ
᪥ᮏ⏕య࢚ࢿࣝࢠ࣮◊✲఍➨ 39 㛤ウㄽ఍ࠊ㟼ᒸࠊ2013 ᖺ 12
᭶
㸶㸬ࡑࡢ௚≉グ஦㡯
㸯㸬እ㒊㈨㔠㸹 ⚾❧኱Ꮫᡓ␎ⓗ◊✲ᇶ┙ᙧᡂᨭ᥼஦ᴗ◊✲
ㄢ㢟ྡ㸸ࢱࣥࣃࢡ㉁ࡢ⏕ᡂ࡜⟶⌮
◊✲௦⾲⪅㸸ྜྷ⏣㈼ྑ 㸦+㸧
⛉Ꮫ◊✲㈝⿵ຓ㔠࣭ᇶ┙◊✲㸦㹑㸧
ㄢ㢟ྡ㸸㸿㹒㹎ྜᡂ㓝⣲ࡢᵓ㐀࡜ไᚚ࡜⏕⌮
◊✲௦⾲⪅㸸ྜྷ⏣㈼ྑ 㸦+㸧
⛉Ꮫ◊✲㈝⿵ຓ㔠 ᪂Ꮫ⾡㡿ᇦ◊✲ࠕኳ↛ኚᛶࢱࣥࣃࢡ㉁ࠖ
ㄢ㢟ྡ㸸ኳ↛ኚᛶࢱࣥࣃࢡ㉁࡜ศᏊࢩࣕ࣌ࣟࣥࡢ┦஫స⏝ࡢ
ゎ᫂
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U"ĮpėēĎěĊĭĉĪĂś+”˜ŜÖ
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ĪđČģĮiĨĉĝēĪĎěĮ‘vĝ”˜ĮÄĤęąĪĂÖ
Research projects and annual reports
Ö
Diversified microorganisms are able to colonize the
531
intercellular, and sometimes also intracellular, spaces of
×ÜØÖ
ÖõóèåÜÝÝ ğ 6ŀıľ
plant tissues, without causing apparent damage to the
×ì÷ÿùúúØĝrS\Į´HēĪĎěĊĚċĜąĂđĉđĜ
host plant. Rhizobia and bacterial endophytes have been
ĊĨā ĥđČğ Į<Œďĕė õóèåÜÝÝ <Œğ
isolated from several tissues in numerous plant species.
ì÷ÿùúú ĝrS\Į´HēĪĂĎīĨĞ<Œğ ôÞóó
Such many bacterial strains have beneficial effects on
ĮS\ĚċĜąėĤāijŋIJĵĿŚĮ‰s…ġ~Ě
plant growth and health. Some strains of them are
ċĜąĂĘĢĩāõóèåÜÝÝ ĚğāijŋIJĵĿŚĞH Ċ
studied in terms of the molecular mechanisms of
ì÷ÿùúú ĞrS\Į^
establishment inside plants and their functions well.
ēĪĎěĮ•đęąĪĂś+
”˜ŜÖ
We reported the full genome sequences of such bacteria,
×ÝØÖ
ïöñÝÛÞâ qЉİıœŘńĞ:
Mesorhizobiumi, Bradyrhizobium, and Azospirillum. The
8ÈĮ}CđėĂïöñÝÛÞâ qЉİıœŘńğŋIJ
genomic information provided valuable insights into the
ņŕİœņŘ Āòïå Æ@ĝcďīėVāÇĝĸŇ
life
ŐŔİŖŘļőŘŃĊ‰ĒęąėĂĎЉİıœŘńğ àÞÞÖ
interactions with host plants. We examine the nucleotide
üø ĞÌďĚĄĩāĖĞÓ7ĝğ àÛß Æ@Ċ‚ďīėĂ
sequences of the other related endophytic bacterial
+—Ğ îåêêÞÛÞÛää qĈħĠ òâå qЉİıœŘń
strains genomes and deduce the symbiotic functional
ěÈ|¿ĮĈĎĜąāÜáà Æ@ĉĨĜĪĹİÓ7Į+
gene repertoire in their genomes. Comparative genomics
CđėĂĢėāïöñÝÛÞ⠆ŒĜrS\ÎÃÆ@
of naturally occurring plant-associated bacteria have a
ĥ°ĘĉĩāĎīĨĊn«qĞQ7F†ŒZĝGē
potential for providing information that can be used to
Īě‚ďīėĂś+”˜ŜÖ
develop enhanced plant-microbe interaction.
×ÞØÖ ğŀıľěЉĮ\šďĕ
(1) A Rj2 soybean plant (Hardee) is symbiotically
ĪĞĝāííí 6~žśôÞóóŜĮ‹ēĪĎěĊĚċĪĂÊ
incompatible with Bradyrhizobium japonicum USDA122.
‰6Ğ ğāïêò <Œŀıľ éýÜÝãÝ Ğrĝ™
The rhizobial rhcJ and ttsI mutants fail to secrete typical
of
the
bacteria,
including
information
about
effector proteins through the type III secretion system
incompatibility with Rj2 soybean plants. Appl. Environ.
(T3SS), and they gain the ability to nodulate Hardee.
This suggests that some effectors secreted via the T3SS
Microbiol. 2013, 79,1048-1051
H. Kasai-Maita, H. Hirakawa, Y. Nakamura, T. Kaneko, K. Miki,
trigger incompatibility between these two partners.
J. Maruya, S. Okazaki, S. Tabata, K. Saeki, S. Sato:
(2) We determined the complete nucleotide sequence of
Commonalities and differences among symbiosis islands of
Mesorhizobium loti strain NZP2037 symbiosis island,
three Mesorhizobium loti strains. Microbes Environ. 2013, 28,
and we compared it with those of strain MAFF303099
275-278
and R7A.
The determined 533 kb sequence of
S. Okazaki, T. Kaneko, S. Sato, K. Saeki: Hijacking of
NZP2037 symbiosis island, on which 504 genes were
leguminous nodulation signaling by the rhizobial type III
predicted,
secretion system. Proc. Natl. Acad. Sci. U S A. 2013, 110,
implied
phenylalanine-tRNA
its
gene
integration
and
into
subsequent
a
genome
rearrangement. The core regions of the three symbiosis
17131-17136
K. Takeshima, T. Hidaka, M. Wei, T. Yokoyama, K. Minamisawa,
islands consisted of 165 genes. NZP2037 specific-genes
H. Mitsui, M. Itakura, T. Kaneko, S. Tabata, K. Saeki, H.
encoding functional proteins in nodulation-related events
Oomori, S. Tajima, T. Uchiumi, M. Abe, Y. Tokuji, T.
were found. They suggest that these specific genes
Ohwada: Involvement of a novel genistein-inducible multidrug
contribute to broaden the host range of NZP2037.
efflux pump of Bradyrhizobium japonicum early in the
(3) Bradyrhizobium elkanii uses the type III secretion
interaction with Glycine max (L.) Merr. Microbes Environ.
system (T3SS) to militate for symbiosis with soybean.
2013, 28, 414-421.
The wild-type strain, but not the T3SS-deficient mutant,
Ö
is able to form nitrogen-fixing nodules on the root of the
730/Ö
soybean nfr mutant En1282. Expression of the soybean
DƒPw, ¬z, NKªw, IJ, 0T, Ë@º
nodulation-specific genes ENOD40 and NIN is increased
şŀıľr« Bradyrhizobium elkaniiĞ|¿ĸŇŐ²oÖ
in the roots of En1282 inoculated with B. elkanii but not
›231s…X‰…”˜€āIJLā2013.9.7-9
with its T3SS mutant.
Therefore, T3SS could activate
Ö
host nodulation signaling by bypassing nod-factor
83.1
recognition.
ŝŜÖ =ǼË
(4) Bradyrhizobium japonicum occurs triggering their
–B”˜»®$Ëř8”˜śçŜÖ
symbiotic interaction with soybean by the detection of
¶Ô,şŏŒĹĶĺ±0ZijŘńŋįıŃĝħĪ‰ĻĽłŐĞ
genistein. A genomic locus (BjG30) that is separated
[98S\Ö
”˜­¥şË@ºÙÖ )WORşìÝàÚÝâ OÖ ×Þ OØÖ
from the symbiosis island is induced the expression
within minutes after the addition of genistein. The
ŞŜÖ Ö ĖĞÖ ĜđÖ
Ö
mRNA levels showed distinct concentration dependence.
This locus contains genes for the multidrug efflux pump,
Ö
TetR
Ö
family
transcriptional
regulator,
and
polyhydroxybutyrate (PHB) metabolism. The deletion of
genes encoding the multidrug efflux pump resulted in
defective
nodulation
performance
and
lower
nitrogen-fixing capability. These results indicate that
BjG30 plays a key role in the early stage of symbiosis as
a nod gene inducer.
Ö
6320/
T. Tsukui, S. Eda, T. Kaneko, S. Sato, S. Okazaki, K.
Kakizaki-Chiba, M. Itakura, H. Mitsui, A. Yamashita, K.
Terasawa, K. Minamisawa: The type III Secretion System of
Bradyrhizobium japonicum USDA122 mediates symbiotic
෸ᩍᤵ㻌 Ἑ㑔᫛
㞟ᅋ㑇ఏᏛ◊✲ᐊ
Assoc㻚㻌Prof. KAWABE, Akira.
㻸㼍㼎㼛㼞㼍㼠㼛㼞㼥㻌㼛㼒㻌㻼㼛㼜㼡㼘㼍㼠㼕㼛㼚㻌㻳㼑㼚㼑㼠㼕㼏㼟㻌
䠍䠊◊✲ᴫせ㻌
㸰㸧
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ᶵᵓࡢゎ᫂ࢆ኱ࡁ࡞ㄢ㢟࡜ࡋ࡚◊✲ࢆ࠾ࡇ࡞ࡗ࡚࠸
ࡿ࡞࡝ᰁⰍయࡢᵓ㐀ࢆ⪃࠼ࡿୖ࡛㠀ᖖ࡟㔜せ࡞せ
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୰࡛ࡢ㢖ᗘࢆ࡝ࡢࡼ࠺࡟ኚ໬ࡉࡏ࡚࠸ࡃࡢ࠿ࢆ᫂ࡽ
ࡍࡿࡇ࡜࡛⏕≀࡟᭷ᐖ࡞ຠᯝࢆࡶࡓࡽࡍࡇ࡜ࡶ᭷
࠿࡟ࡍࡿࡇ࡜ࡣ㞟ᅋ㑇ఏᏛࡢ୺せ࡞┠ⓗ࡛࠶ࡾࠊ㐣
ࡾࠊከࡃࡢ⏕≀࡛㌿⛣ᅉᏊࢆ୙ά໬ࡍࡿᶵᵓࡀ㐍
ཤ࡟㉳ࡇࡗࡓฟ᮶஦ࢆ᥎ ࡍࡿࡇ࡜࡛⌧ᅾ㐍⾜୰ࡢ
໬ࡋ࡚࠸ࡿࠋ⌧ᅾࠊࢩࣟ࢖ࢾࢼࢬࢼ࡛᭱㏆᫂ࡽ࠿
㐍໬ࡸᑗ᮶ⓗ࡟࡝ࡢࡼ࠺࡟㐍໬ࡀ㉳ࡇࡿࡢ࠿ࢆண ࡟࡞ࡗࡓ㌿⛣άᛶࢆᣢࡘ㌿⛣ᅉᏊ࡟ࡘ࠸࡚ࠊ࢔ࣈ
ࡍࡿࡇ࡜ࡀ࡛ࡁࡿࠋ
ࣛࢼ⛉ࡢ୰࡛ࡢ㐍໬ࣃࢱ࣮ࣥࢆゎᯒࡍࡿࡇ࡜࡛࡝
ᮏ◊✲ศ㔝࡛ࡣ≉࡟ᰁⰍయᵓ㐀ࡢ㐪࠸ࡸࡑࢀࢆࡶ
ࡢࡼ࠺࡟ࢥࣆ࣮ᩘࢆቑࡸࡋ୙ά໬ࢆࡲࡠࡀࢀ࡚࠸
ࡓࡽࡍᶵᵓࡀ࡝ࡢࡼ࠺࡟ '1$ ኚ␗࡟ᙳ㡪ࢆ୚࠼ࡿ࠿
ࡿࡢ࠿࡞࡝࡟ࡘ࠸࡚᫂ࡽ࠿࡟ࡋࡼ࠺࡜ࡋ࡚࠸ࡿࠋ
࡜࠸࠺Ⅼ࡟↔Ⅼࢆ⤠ࡗ࡚◊✲ࢆ࠾ࡇ࡞ࡗ࡚࠸ࡿࠋࢤ
㸱㸧
ࣀ࣒࡟ࡣከࡃࡢ㑇ఏᏊࡀᏑᅾࡋࠊࡑࢀࡒࢀࡀ⮬↛㑅
࢚ ࣆ ࢪ ࢙ࢿ ࢸ࢕ ࢵ ࢡ࡞ ไ ᚚᶵ ᵓ ࡢ 㐍໬࡟
୚࠼ࡿᙳ㡪ࡢゎ᫂
ᢥࡢᑐ㇟࡜࡞ࡗ࡚⏕≀ࡢ㐍໬ࡢせᅉ࡜࡞ࡗ࡚࠸ࡿࠋ
࢚ࣆࢪ࢙ࢿࢸ࢕ࢵࢡ࡞ไᚚᶵᵓ࡟ࡼࡾ㑇ఏᏊⓎ
ࡋ࠿ࡋ඲࡚ࡢ㑇ఏᏊࡣྠᵝ࡟⮬↛㑅ᢥࡢᙳ㡪ࢆཷࡅ
⌧ࡸࢡ࣐ࣟࢳࣥᵓ㐀ࡢኚ໬ࡀ㉳ࡇࡿࡇ࡜ࡀ▱ࡽࢀ
ࡿࢃࡅ࡛ࡣ࡞ࡃࠊ࿘㎶ࡢ㡿ᇦࡢᰁⰍయᵓ㐀ࡢ㐪࠸࡟
࡚࠸ࡿࠋ࢚ࣆࢪ࢙ࢿࢸ࢕ࢵࢡ࡞ไᚚࡣ㓄ิࡢ㐪࠸
ࡼࡗ࡚⮬↛㑅ᢥࡢാࡃᗘྜ࠸ࡣ␗࡞ࡗ࡚ࡃࡿࠋ༢⣧
࡟ࡼࡽࡎ⾲⌧ᙧ࡟ᕪ␗ࢆࡶࡓࡽࡍࡇ࡜ࡀྍ⬟࡛࠶
࡞ࡶࡢ࡛ࡣࠊ㡿ᇦ㛫࡛⤌᥮࠼⋡ࡀ㐪࠺࡜㐃㙐ࡢᙉࡉ
ࡿࡀࠊࢡ࣐ࣟࢳࣥᵓ㐀ࡢኚ໬࡟ࡼࡾ㐍໬ࣃࢱ࣮ࣥ
࡟ᕪࡀ⏕ࡌࠊ⮬↛㑅ᢥࡢຠᯝࡀ㡿ᇦ࡟ࡼࡗ࡚኱ࡁࡃ
࡟ᙳ㡪ࢆ୚࠼ࡿ࡜ᛮࢃࢀࡿࠋᵝࠎ࡞࢚ࣆࢪ࢙ࢿࢸ
␗࡞ࡿࡇ࡜࡟࡞ࡿࠋᰁⰍయࢆᵓᡂࡍࡿせ⣲࡛࠶ࡿື
࢕ࢵࢡไᚚᶵᵓࡢ࠺ࡕ≉࡟ࢤࣀ࣒࢖ࣥࣉࣜࣥࢸ࢕
ཎయࡸࢸ࣓ࣟ࢔࡞࡝ࠊࡲࡓ࣊ࢸࣟࢡ࣐ࣟࢳࣥࢆᵓᡂ
ࣥࢢ࡟ὀ┠ࡋ࡚◊✲ࢆ㐍ࡵ࡚࠸ࡿࠋ࢖ࣥࣉࣜࣥࢸ
ࡍࡿ㌿⛣ᅉᏊ࡞࡝ࠊ࢚ࣆࢪ࢙ࢿࢸ࢕ࢵࢡ࡞ࢡ࣐ࣟࢳ
࢕ࣥࢢไᚚࣃࢱ࣮ࣥࡢኚ໬ࡸ࢖ࣥࣉࣜࣥࢸ࢕ࣥࢢ
ࣥᵓ㐀ࡢኚ໬࡞࡝ࠊࡣ࿘㎶㡿ᇦࡢ㐍໬ࣃࢱ࣮ࣥࢆỴ
ࢆཷࡅࡿࡇ࡜࡟ࡼࡿ㐍໬࡬ࡢᙳ㡪࡞࡝ࢆㄪᰝࡋ࡚
ᐃࡍࡿୖ࡛㠀ᖖ࡟㔜せ࡞ࡶࡢ࡛࠶ࡿࠋ༢࡟⾲⌧ᙧࡢ
࠸ࡿࠋ
ኚ໬ࢆࡶ࡜࡟⮬↛㑅ᢥࡢ᳨ฟࡸ㐺ᛂ㐍໬ࡢண᝿ࢆࡍ
㻌
ࡿࡢ࡛ࡣ࡞ࡃࠊࡑࡶࡑࡶ⮬↛㑅ᢥࡢᙳ㡪ࡀ࡝ࡢࡼ࠺
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
࡞せᅉ࡟ࡼࡗ࡚ኚ໬ࡍࡿࡢ࠿ࢆ᫂ࡽ࠿࡟ࡍࡿࡇ࡜ࡣࠊ
ᮏᖺᗘࡣືཎయࡢ㐍໬ᶵᵓࡢゎ᫂ࡢࡓࡵ࡟ࠊືཎ
㏆ᖺࡢࢤࣀ࣒᝟ሗࢆࡶ࡜࡟ࡋࡓ⏕≀ᏛࡢⓎᒎࢆ㋃ࡲ
యᵓᡂࡢ␗࡞ࡿ⣔⤫㛫࡛సฟࡋࡓ㹄㸯ࡢᰁⰍయࡢఏ
࠼࡚ከᵝᛶ◊✲ࢆࡍࡿ࠺࠼࡛ࡣḞ࠿ࡏ࡞࠸ࡶࡢ࡟࡞
㐩⋡ࡢㄪᰝࢆ࠾ࡇ࡞ࡗ࡚࠸ࡿࠋ๓ᖺᗘ࡟࠾ࡇ࡞ࡗࡓ
ࡗ࡚ࡃࡿ࡜ᛮࢃࢀࡿࠋ
஺㓄࡟ࡼࡿḟୡ௦࡬ࡢఏ㐩⋡ࡢㄪᰝ࡟ຍ࠼࡚ῶᩘศ
ᮏ◊✲ศ㔝࡛ࡣලయⓗ࡟ḟࡢ㸱Ⅼ࡟ࡘ࠸࡚◊✲ࢆ
⿣᫬ࡢఏ㐩ᵝᘧࡢゎᯒࢆ࠾ࡇ࡞ࡗࡓࠋ
㐍ࡵ࡚࠸ࡿࠋ
㸯㸧
ືཎయ㡿ᇦࡢ㐍໬ᶵᵓ
㌿⛣ᅉᏊࡢゎᯒ࡟㛵ࡋ࡚ࡣࠊࢩࣟ࢖ࢾࢼࢬࢼ࡛㌿
⛣ ά ᛶ ࡀ ☜ ㄆ ࡉ ࢀ ࡓ 㹒 㹇 㹐 7HUPLQDO ,QYHUWHG
ືཎయࡣ⣽⬊ศ⿣ࡢ㝿࡟ᰁⰍయࢆṇ☜࡟ፉ⣽⬊
5HSHDWࡢ࡞࠸㹋㹓㹊㹃࡛࠶ࡿ㹔㸿㹌㹂㸿㹊ࣇ࢓࣑
࡟ศ㓄ࡍࡿࡓࡵ࡟ᚲ㡲ࡢࡶࡢ࡛࠶ࡾࠊ㑇ఏ᝟ሗࡢ
࣮ࣜࡢ㌿⛣ᶵᵓࡢゎ᫂ࢆ࠾ࡇ࡞ࡗࡓࠋ㹔㸿㹌㹂㸿㹊
ṇ☜࡞ఏ㐩࡟ࡣ୙ྍḞࡢࡶࡢ࡛࠶ࡿࠋࡋ࠿ࡋࠊࡑ
ࣇ࢓࣑࣮ࣜࡣᮎ➃ࡢ཯᚟㓄ิࢆḞ࠸࡚࠸ࡿࡀษࡾฟ
ࡢ㔜せᛶ࡟ࡶࡼࡽࡎືཎయ㓄ิࡣࢤࣀ࣒୰࡛᭱ࡶ
ࡋ࡜ᤄධࡣṇᖖ࡟㉳ࡇࡿࠋ㹔㸿㹌㹂㸿㹊ࣇ࢓࣑࣮ࣜ
᪩ࡃ㐍໬ࡍࡿ࡜ゝࢃࢀ࡚࠸ࡿࠋࢩࣟ࢖ࢾࢼࢬࢼࡢ
ࡀᣢࡘ㸱ࡘࡢ㑇ఏᏊࡢᙺ๭ࢆ᫂ࡽ࠿࡟ࡍࡿࡓࡵ࡟ࡑ
㏆⦕✀ࢆ⏝࠸࡚ືཎయ㓄ิࡀ࡝ࡢࡼ࠺࡟⨨᥮ࡋ࡚
ࢀࡒࢀࡢ㑇ఏᏊࡢᑟධಶయࢆసᡂࡋࡓ࡜ࡇࢁࠊࡇࢀ
࠸ࡿࡢ࠿ࠊືཎయ㓄ิࡢ㐪࠸ࡀᐇ㝿࡟ᰁⰍయࡢศ
ࡲ࡛ᶵ⬟ࡀᮍ▱࡛࠶ࡗࡓ㑇ఏᏊࡀ㹔㸿㹌㹂㸿㹊ࡢ࣓
㞳࡟ᙳ㡪ࢆ୚࠼ࡿࡢ࠿ࢆゎᯒࡋ࡚࠸ࡿࠋ
ࢳࣝ໬ࣞ࣋ࣝࢆపୗࡉࡏࡿࡇ࡜࡟ࡼࡾࡇࡢ㌿⛣ᅉᏊ
ࡢ෌άᛶ໬⬟ࢆᣢࡘࡇ࡜ࡀ᫂ࡽ࠿࡟࡞ࡗࡓࠋ෌άᛶ
We focused on the maintenance mechanisms of DNA
໬⬟ࡣࡑࡢࢥࣆ࣮࡟㓄ิࡢ┦ྠᛶࡀ㧗࠸ࡶࡢࢆ≉␗
variation in Plant species. We are interested in the
ⓗ࡟ㄆ㆑ࡋ࡚࠸ࡿྍ⬟ᛶࡀ᭷ࡾࠊࡇࢀࡲ࡛Ⰻࡃࢃ࠿
following four topics.
ࡗ࡚࠸࡞࠿ࡗࡓ㌿⛣ᅉᏊࡢ฼ᕫⓗ࡞ቑᖜᶵᵓࡸࠊ㌿
⛣ᅉᏊࡢไᚚᶵᵓࡢ⌮ゎ࡟㈉⊩ࡍࡿࡇ࡜ࡀᮇᚅࡉࢀ
1) Evolutionary process of Centromere regions
ࡿࠋࡇࡢࡼ࠺࡞෌άᛶ⬟ࡢ࠶ࡿ㑇ఏᏊࡢᏑᅾࡸࠊᐟ
Centromere
is
an
important
area
for
accurate
୺ࡢᢚไᶵᵓࡢࢱ࣮ࢤࢵࢺ࡜࡞ࡾ࠺ࡿ཯᚟㓄ิࡢḞ
chromosome segregation but is also one of the fastest
ዴࡣࠊ௚ࡢ㹋㹓㹊㹃࡟ẚ࡭࡚㹔㸿㹌㹂㸿㹊ࣇ࢓࣑ࣜ
evolving regions in the genome. By using Arabidopsis
࣮ࡀ㧗࠸ቑᖜ⬟ࢆᣢࡘࡇ࡜ࡢ୍ᅉ࡜࡞ࡗ࡚࠸ࡿྍ⬟
relatives,
ᛶࡀ࠶ࡿ㸦ᅗ㸯㸧ࠋ
centromeric sequences on the segregation ratio. We made
we
are
analyzing
effect
of
different
F2 plants with different centromere organization patterns
to analyse transmission rate of each chromosome.
2) Patterns of Transposable Element Evolution
In Arabidopsis thaliana, several transposable element
families were identified to have active transposability.
We analysed evolution of ONSEN family transposons.
We found wide distribution of ONSEN family and
conservation of heat activation among Brassicaceae.
3) Effect of Epigenetic regulation on Evolution
Epigenetic regulation can affect evolution patterns
through change of chromatin structure. We focused on
imprinting genes to analyse divergence patterns. We
ᅗ䠍㻌 䠲䠝䠪䠠䠝䠨䝣䜯䝭䝸䞊䜢ྵ䜐䠩䠱䠨䠡䛾ศᏊ⣔⤫ᶞ
detected
䠄㉥⥺䛿䠝䠊䡈䡕䡎䠽䡐䠽䚸㯮⥺䛿䝅䝻䜲䝚䝘䝈䝘⏤᮶䛾䜒䛾䠅㻌
conservation of gene structure between epigenetically
㻌
regulated and non-epigenetically regulated loci.
differences
in
duplication
numbers
and
䝅䝻䜲䝚䝘䝈䝘䛷䜲䞁䝥䝸䞁䝔䜱䞁䜾䛜ሗ࿌䛥䜜䛶䛔䜛
㑇ఏᏊ⩌䛻䛴䛔䛶ศᏊ㐍໬Ꮫⓗゎᯒ䜢䛚䛣䛺䛔䚸๓ᖺ
4) Evolution of nuclear transferred cytoplasmic genome
ᗘ䛻䜲䞁䝥䝸䞁䝔䜱䞁䜾䛸㑇ఏᏊ㔜」䛻㛵㐃䛜䛒䜛䛣䛸䜢
DNAs
♧၀䛧䚸䜎䛯䜲䞁䝥䝸䞁䝔䜱䞁䜾㑇ఏᏊ䛾㐍໬䛜௚䛾㑇ఏ
We analysed patterns of nuclear plastid DNA-like
Ꮚ䛸䛿␗䛺䜛䛣䛸䜢ぢฟ䛧䛯䚹ᮏᖺᗘ䛿䛣䛾⌧㇟ 䜢᳨ド
sequences (NUPT) in several plant species. We found
䛩䜛䛯䜑䛻␗䛺䜛⏕≀䛷ᐇ㦂ゎᯒ䜢䛚䛣䛺䛔䚸䜲䞁䝥䝸䞁
age
䝔䜱䞁䜾䛥䜜䜛㑇ఏᏊ䛾㐍໬䝟䝍䞊䞁䛾୍⯡ᛶ䜢᫂䜙䛛
distribution of NUPTs among species. The findings will
䛻䛧䛯䚹䜎䛯᰾䝀䝜䝮䛻Ꮡᅾ䛩䜛䜸䝹䜺䝛䝷䝀䝜䝮⏤᮶㓄
contribute
ิ䛾㐍໬䝟䝍䞊䞁䛾ゎᯒ䜢䛚䛣䛺䛔䚸䜸䝹䜺䝛䝷䛛䜙᰾
mechanisms about evolution of cytoplasmic genome
䜈䛾㌿⛣ᚋ䛻㉳䛣䜛✺↛ኚ␗䛻䛿ㄪᰝ䛧䛯᳜≀඲䛶䛷
fragment after transferred to nuclear genome.
ඹ㏻䛩䜛೫䜚䛜ぢ䜙䜜䜛䛣䛸䜢᫂䜙䛛䛻䛧䛯䚹䛣䛾೫ 䜚䛿
㻌
㌿⛣᫬ᮇ䛻䜘䛳䛶␗䛺䛳䛶䛚䜚䚸᰾䛻Ꮡᅾ䛩䜛䜸䝹䜺䝛
䠐䠊ㄽᩥ䠈ⴭ᭩䛺䛹㻌
䝷䝀䝜䝮᩿∦䛿ఱ䜙䛛䛾ᙧ䛷ㄆ㆑䛥䜜䚸೫䛳䛯✺↛ኚ␗
H. Ito, T. Yoshida, S. Tsukahara, A. Kawabe: Evolution of the
䛜㉳䛣䜛䛣䛸䛜♧၀䛥䜜䛯䚹⌧ᅾ䚸䛣䛾೫䜚䛸᫬㛫ⓗ䛺ኚ
ONSEN retrotransposon family activated upon heat stress in
໬䜢㉳䛣䛩ཎᅉ䛻䛴䛔䛶ゎᯒ䜢㐍䜑䛶䛔䜛䚹㻌
㻌
㸱㸬Research projects and annual reports
dependent
degradation
understanding
of
patterns
general
and
biased
maintenance
Brassicaceae. Gene. 2013. 518, 256-261
Y. Fu, A. Kawabe, M. Etcheverry, T. Ito, A. Toyoda, A. Fujiyama,
V. Colot, Y. Tarutani, T. Kakutani: Mobilization of a plant
transposon by expression of the transposon-encoded
anti-silencing factor. EMBO J. 2013. 32, 2407-2417
T. Yoshida, A. Kawabe: Importance of Gene Duplication in the
䠏䠅㻌 䛭䛾௚㻌 䛺䛧㻌
Evolution of Genomic Imprinting Revealed by Molecular
㻌
Evolutionary Analysis of the Type I MADS-Box Gene Family
㻌
in Arabidopsis Species. PLOS One. 2013. 2, e73588
T. Yoshida, HY. Furihata, A. Kawabe: Patterns of genomic
integration of nuclear chloroplast DNA fragments in plant
species. DNA Research, published online ahead of print 2013
Oct 29
Ἑ㑔᫛䚸㧗㔝ᩄ⾜㻦㻌 ✺↛ኚ␗䠄䠏䠅㑇ఏⓗከᆺ㻚㻌 㑇ఏᏊᅗ㚷
䠄ᅜ❧㑇ఏᏛ◊✲ᡤ䛂㑇ఏᏊᅗ㚷䛃⦅㞟ጤဨ఍䠅㻌 㻞㻜㻝㻟 㻘㻌
㻝㻠㻢㻙㻝㻠㻣㻌
㻌
䠑䠊Ꮫ఍Ⓨ⾲䛺䛹㻌
ྜྷ⏣㈗ᚨ䚸Ἑ㑔᫛: 䝀䝜䝮䜲䞁䝥䝸䞁䝔䜱䞁䜾䛥䜜䜛type I
MADS-box㑇ఏᏊ䛾㑇ఏᏊ㔜」䛸ศᏊ㐍໬.᪥ᮏ㐍໬Ꮫ఍➨
15ᅇ䛴䛟䜀኱఍䠈⟃Ἴᕷ䠈2013.8.28-31
ᑠᮡளᕼ䚸⏣୸₶䚸ᚋ⸨࿴⨾䚸ΎỈ㢧ྐ䚸Ἑ㑔᫛䚸ཎ⏣ⱥ⨾Ꮚ:
ఀ྿ᒣ䛾▼⅊▼᥇᥀ሙ䛻⏕⫱䛩䜛Arabidopsis halleri ssp.
gemmifera 䛾2䛴䛾⏕ែᆺ䛻䛚䛡䜛㔠ᒓ⵳✚. ᪥ᮏ᳜≀Ꮫ఍
➨77ᅇ኱఍䠈ᮐᖠᕷ䠈2013.9.13-15
௜䜖䛖䚸Ἑ㑔᫛䚸ఀ⸨䛯䛩䛟䚸㇏⏣ ᩔ䚸⸨ᒣ⛅బኵ䚸ᶡ㇂ⰾ᫂䚸
ゅ㇂ᚭோ: 䝅䝻䜲䝚䝘䝈䝘TE䛾ᢚไゎ㝖άᛶ.᪥ᮏ㑇ఏᏛ఍
➨85ᅇ኱఍䠈ᶓ὾ᕷ䠈2013.9.19-21
ྜྷ⏣㈗ᚨ䚸㝆᪝ึె䚸ゅ㇂ᚭோ䚸Ἑ㑔᫛: ᰾䛻⛣⾜䛧䛯ⴥ⥳య
䝀䝜䝮᩿∦䛾䜶䝢䝆䜵䝛䝔䜱䝑䜽䛺ಟ㣭䛸ศᏊ㐍໬. ᪥ᮏ㑇ఏ
Ꮫ఍➨85ᅇ኱఍䠈ᶓ὾ᕷ䠈2013.9.19-21
㝆᪝ึె䚸ྜྷ⏣㈗ᚨ䚸Ἑ㑔᫛: 䝅䝻䜲䝚䝘䝈䝘ᒓ᳜≀䛻䛚䛡䜛ᰁ
Ⰽయఏ㐩⋡䛾೫䜚䜈䛾ືཎయ㓄ิ䛾ᙳ㡪. ᪥ᮏ㑇ఏᏛ఍➨
85ᅇ኱఍䠈ᶓ὾ᕷ䠈2013.9.19-21
Ἑ㑔᫛䚸ゅ㇂ᚭோ: ືཎయ䜢䝍䞊䝀䝑䝖䛸䛩䜛LTRᆺ䝖䝷䞁䝇䝫䝌
䞁. ᅜ❧㑇ఏᏛ◊✲ᡤ◊✲㞟఍䛂㌿⛣ᅉᏊ䛸ᐟ୺䛾┦஫స⏝
䛻䜘䜛⏕࿨ᶵ⬟䛃䠈୕ᓥᕷ䠈2013.10.10-11
㻌
䠒䠊䛭䛾௚≉グ஦㡯㻌
䠍䠅㻌 እ㒊㈨㔠
⛉Ꮫ◊✲㈝⿵ຓ㔠䞉᪂Ꮫ⾡㡿ᇦ◊✲䠄ィ⏬⌜䞉ศᢸ䠅㻌
ㄢ㢟ྡ䠖䜲䝛ᒓ⬇ங䛻䛚䛡䜛∗䞉ẕ䝀䝜䝮䛾䜶䝢䝆䜵䝛䝔䜱䝑䜽
䛺ㄪ࿴䛸㌵㎚䛾ศᏊᶵᵓ㻌
◊✲௦⾲⪅䠖ᮌୗဴ㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻟㻙㻞㻣 ᖺ㻌 㻔䠑ᖺ㻕㻌
ᅜ❧㑇ఏᏛ◊✲ᡤඹྠ◊✲䠝㻌
ㄢ㢟ྡ䠖䝅䝻䜲䝚䝘䝈䝘㏆⦕✀䛻䛚䛡䜛㌿⛣ᅉᏊ䛾ไᚚᶵᵓ
䛾ゎ᫂㻌
◊✲௦⾲⪅䠖Ἑ㑔᫛㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻡 ᖺ㻌 㻔㻝 ᖺ㻕㻌
䠎䠅㻌 Ꮫእάື㻌 䠣䡁䡊䡁䡐䡅䠿䠽䠖⦅㞟ጤဨ㻌
㻌
◊✲ᐊ㞟ྜ෗┿㻌
㻌
"#+-".+-0+%!("*.$/$(+,)$*."('+(+&0
Associate Prof. Seisuke Kimura, Ph. D.ƈ
76
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図1 ニューベキア（Rorippa aquatica）
左：陸上の形態 左：水中の形態
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most of lake cress populations are found. Despite the
ǛNJƏƐƎĖǭƛƙƨƫȬȺȈȺȀ¥ǛǡNjƗƒ$ǓǺǫǼƞ Ɛ
significance
7 Ɓ ƀ ^ ǭȓȆȣȘȄȥȸȍǩĽ • ǭz Ų ʼn Æ ȀĿ ǏȽ
mechanisms of phenotypic plasticity and environmental
ƩƬƤʼnÆȀǛǡǩǘǾNJƔþǩƏƎþǭÇĹȻšŵĬȼǬp
responses in plants, the underlying mechanism hasn't been
ǕǫȥȺȌǔņǺǽǡNjǘǽǺǭŨt“ȀʼnÆǝǼǘǩǨNJ
investigated. We investigate the mechanism of the
Ľǭ•£ÝzŨtȀPzǨǕǼǩ½™ǙǽǼNjƈ
heterophylly of lake cress.
of
this
plant
to
study
fundamental
We hypothesized that phytohormones have important
roles in determination of leaf shape of lake cress. Thus, we
quantified various phytohormones in leaf primordia by
liquid chromatography-tandem mass spectrometry. We
found that gibberellin and jasmonic acid were more
abundant when they develop simple leaves than compound
ミズナ ミズナとミブナのF1
ミブナ 打木源助 エベレスト
leaves. We also found that application of gibberellin to
ダイコン
shoot apex can dramatically change leaf shape of lake
図2 野菜に観察される葉形の多様性
cress. These results suggested that gibberellin, at least, is
ƈ ƉƑƊƈ ÌïǔȎȣȮȀwǼǛǖǴǭďėƈ
ƈ ƜƦƙ¯) ĜǮNJƜƦƙſ}ǫǪǭÿȀĆŇǛǧĠĴ
T½Ȁ&ÖǙǟǡǻNJĠĴÙȀŌ‚ǝǼÔÒǨǎǼNj@ï
ǨǮȉȸ¨<ŨtǭƾƓƑǔȬȔȘȺȶȋȲȶȺȘȺǩǛǧ
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ǏǫǓǤǡNjē ť ǮNJƫƧƟƏǩǏǐÌ ï ò Ķ ǭȚȆțȌȫȄ
ȸȞ]tǔNJÌïǭƜƦƙ¯) ĜǭȬȔȘȺȶȋȲȶȺȘ
ȺǩǛǧ*ǏǧǏǼǘǩȀņǏǢǛȽƫƧƟƏǭÔĵʼnÆȀŢ
ǶǧǏǼNjƫƧƟƏǮř5]tǨǎǼǔNJǭľăŗǩĉ
úǛǫǔǺÔĵǛǧǏǼǩįǑǺǽǼǡǶȽ.āÞŻá
ǩŗ Ų 7 Æ ǬǹǻNJĉ ú ] t ǭP z Ȁŋ ǴǡNjLjĨ
î  ǬǹǼƜƦƙ¯ ) Ō ‚ š ǬƫƧƟƏǩĢ N ǝǼ] t ǸȽ
ŞǬʼnƁǝǼ]tȀń±PzǝǼǘǩǔǨǕǡNjõaNJǘ
ǽǺǭ]tǭÔĵʼnÆȀǒǘǫǤǧǏǼNjƈ
interested
in
plant
in
leaves.
This
phenomenon
is
called
‘compensation’. We happened to notice that leaf cells of
lake cress showed compensation reaction when they are
grown at relatively low temperature. This is the first
finding
that
compensation
reaction
is
induced
by
environmental cue, and we are now investigating the
mechanism of the reaction.
(2) The evolutinary-developmental study on leaf shape
Cultivated vegetables show remarkable variation in leaf
morphology. For example, Mizuna (Brassia rapa var.
nipponsinica) has deeply lobed leaves, while Mibuna (B.
rapa var laciniifolia), which is developed from Mizuna by
shape variation. Based on RNA-seq data of Mizuna and
development
and
environmental interactions. Currently, we have been
focusing on the following four major projects.
Mibuna, we developed more than 120 CAPS markers.
Then Ninety-four F 2 individuals from cross between
Mizuna and Mibuna were analyzed for segregation at 120
(1) Analysis of Phenotypic Plasticity of Leaf shape of
Lake cress
CAPS loci and for variation in leaf shape. Two putative
quantitative trait loci (QTL) were detected for the leaf
Plant can alter their development, physiology and life
history depending on environmental conditions. This
fundamental property is called phenotypic plasticity. The
North American lake cress, Rorippa aquatica, shows
heterophylly,
expansion
margin. We are interested in genetic basis of this leaf
Research projects and annual reports
are
A defect of cell proliferation often triggers enhanced cell
breeding in 19th century, has entire leaves with smooth
ƈ
We
involved in heterophylly of lake cress.
phenotypic
plasticity
on
leaf
shape.
Submerged leaves are usually deeply dissected and has
needle-like blade, whereas emergent leaves are generally
entire with serrated or smooth margins. This heterophylly
is thought to be adaptive response to submergence and
increase the fitness in water's edge environment where
shape variation.
(3) Analysis of genome maintenance mechanisms of plants
Arabidopsis SOG1, which is unique to plants, is a master
transcriptional regulator of the DNA damage response. To
identify interacting proteins of SOG1, we performed
co-immunoprecipitaion and mass-spectorometric analysis.
We found multiples proteins which associate with or
dissociate from SOG1 specifically after induction of DNA
damages by gamma-irradiation.
96532
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k‹’dv¦¡w^~^TV6:P>I™»`
Kaoru O Yoshiyama, Junya Kobayashi, Nobuo Ogita, Minako
Ueda,
Seisuke
Kimura,
Hisaji
Maki,
Masaaki
Umeda:
¿¾(8FLµˆ¬±+[­‡mÉ^Ào
Ë:UK;4LÌ
ATM-mediated phosphorylation of SOG1 is essential for the
Ľ ǭ • £ Ǭ Ł õ e M i ¡ Ȁ đ ǝ Ƞ Ȳ Ⱥ ȩ Ȋ Ȃ Ȼ DNA damage response in Arabidopsis. EMBO Reports 14:
! ȼǔo Ó ǫĽ • Ȁø Ǵ6 ǝȯȈȠȕȮǬǥǏǧǭö
817-822 (2013)
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Daniel Koenig*, José M. Jiménez-Gómez*, Seisuke Kimura§,
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V.
Tat,
Takayuki
Tohge,
Anthony
Bolger,
Peng, Neelima R. Sinha, and Julin N. Maloof (*§ These authors
ĖvĚ ƏƐƒ \őìNJƇ/‰pvNJƐƎƏƑƍƏƎƍƏƏƌƏƒƈ
contributed equally to this work): Comparative transcriptomics
Ìïǭ ƜƦƙ ¯)ȚȆțȌȫȄȸȞ]t ƫƧƟƏ Ǯ@ïȉȸ¨<Ũ
reveals patterns of selection in domesticated and wild tomato.
t ƾƓƑ ǭȈȅȸȘȺȤȺȞǓɂNJ¢†ũNJċ¾€àNJËû
Proc. Natl. Acad. Sci. USA 110: E2655-2662 (2013)
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Molly Sharlach, Douglas Dahlbeck, Lily Liu, Joshua Chiu, José
vµOȊȱȸȤȔNJƐƎƏƑƍƗƍƏƗƌƐƏƈ
M. Jiménez-Gómez, Seisuke Kimura, Daniel Koenig, Julin N.
COVJ52+¼+©¦Ä¯*!$0½¢njp‚+M
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RXopJ4, a bacterial spot disease resistance locus from Solanum
?>I Æ_vE>ATV6".s´ºg…,i
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601-609 (2013)
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damage response in plants: Conserved and variable response
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compared to animals. Biology 2: 1338-1356 (2013) (Review)
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÷kǬ ǜǧĽǭ•£ȀmǑǼÌïȠȲȺȩȊȂȀúǏǡȞȳ
of lake cress, Hokuto Nakayama, Seisuke Kimura, The 31 st
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Plant Biotechnology Symposium Program, International Plant
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ື≀ศᏊ⏕ែᏛ◊✲ᐊ
Associate Prof. Jun-ichi Takahashi
Ph.D
Laboratory of Animal Molecular Ecology
䠍䠊◊✲ᴫせ
⋓䛧䛯䚹ᤕ⋓䛧䛯ಶయ䛾యⰍ䛚䜘䜃እ㒊ᙧែ䛜᪥ᮏ䛻
᪻⹸䜔ື ≀䜢◊✲ᑐ ㇟䛸䛧䛶䚸ື≀䛾♫ ఍䛻䛚䛡䜛
⏕ ᜥ 䛩 䜛 7 ✀ 䛾 䝇 䝈 䝯 䝞 䝏 䛾 䛹 䜜䛸 䜒 ␗ 䛺䛳 䛶䛚 䜚 䚸
♫఍ᛶ㐍໬䚸᳜≀䛸䛾ඹ㐍໬䚸✀ศ໬䛾䝯䜹䝙䝈䝮䛾ゎ
Archer (2012)䛜グ㏙䛧䛯䝒䝬䜰䜹䝇䝈䝯䝞䝏䛾ᣢ䛴」ᩘ
᫂䜢┠ⓗ䛻ศᏊ⏕ែᏛⓗ◊✲䜢⾜䛳䛶䛔䜛䚹䛥䜙䛻䝭䝒
䛾ᙧែⓗ≉ᚩ䛜ほᐹ䛥䜜䛯䚹ᤕ⋓䛧䛯ಶయ䛿䚸㢌㒊䛛䜙
䝞䝏䜔䝬䝹䝝䝘䝞䝏䛾㎰ᴗ฼⏝䜢┠ⓗ䛸䛧䛯ᛂ⏝⏕ែ
⭡㒊๓➃ 㒊ศ䛷㯮Ⰽ䛜ᙉ䛟䚸⭡㒊୰䞉ᚋ➃䛚䜘䜃⬮䛾
Ꮫⓗ◊✲䚸⤯⁛䛜༴᝹䛥䜜䛶䛔䜛᪻⹸䞉ື≀㢮䛾ಖㆤ䜢
ᮎ➃㒊 ศ䛜㯤Ⰽ䛸䛔䛖≉ ᚩ䛜ほᐹ䛥䜜䛯䚹㢌 ᴙ䛾ᙧែ
┠ⓗ䛸䛧䛯ಖ඲㑇ఏᏛⓗ◊✲䜢⾜䛳䛶䛔䜛䚹
䛿䚸䝒䝬䜰䜹䝇䝈䝯䝞䝏䛾≉ᚩ䛷䛒䜛ṑ≧✺㉳䛾㝯㉳䛜
䜋䛸䜣䛹䛺䛟䚸ഃṑ䛿୸䛟䛺䛳䛶䛔䛯䚹ゐゅ䛾⠇ᩘ䛿 12
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ
䛷䛒䜚䚸⭡㒊ᮎ➃䛻䛿㔪䛜☜ㄆ䛥䜜䛯䛯䜑㞤ಶయ䛷䛒䛳
䠍䠖ᅾ᮶䝬䝹䝝䝘䝞䝏䛾 DNA ⫱✀
䛯䚹๓⬚⫼ᯈ䛾๓⬚⫼ഃ㠃ୗ㒊䛾๓⬚ᚋⴥ∦䛻䛒䜛⦭
እ᮶✀䛾䝉䜲䝶䜴䜸䜸䝬䝹䝝䝘䝞䝏䛻᭰䜟䜛䝖䝬䝖⏝
ྜ⥺䛸䛔䛟䛴䛛䛾㝯㉳⥺䛜䚸୙᫂░䛷䛒䛳䛯䛣䛸䛛䜙䜒ᮏ
䝫䝸䝛䞊䝍䞊䛸䛧䛶໭ᾏ㐨䛻ᗈ䛟ศᕸ䛩䜛䜶䝌䝖䝷䝬䝹䝝
✀䛾≉ᚩ䜢♧䛧䛶䛔䛯䚹㡑ᅜ䛸ᑐ㤿䛾㛫䛻䛿䚸1993 ᖺ䛛
䝘䝞䝏䚸䜶䝌䝘䜺䝬䝹䝝䝘䝞䝏䚸䜶䝌䜸䜸䝬䝹䝝䝘䝞䝏
䜙㤿ᒣ 䛚䜘䜃㔩ᒣ 䛸ཝཎ 䛾㛫䛷ᐃᮇ⯟㊰䛜㛤タ
䛾 3 ✀䛻ᑐ䛧䛶䚸㑇ఏᏊ᝟ሗ䛻ᇶ䛵䛟 DNA ⫱✀ἲ䜢㐺
䛥䜜䚸┤᥋≀㈨䛜ᣢ䛱㎸䜎䜜䛶䛔䜛䚹㡑ᅜ䛷䛿䚸㔩ᒣᕷ
⏝䛧䚸䝉䜲䝶䜴䜸䜸䝬䝹䝝䝘䝞䝏䛾௦᭰✀䛸䛧䛶฼⏝䛧ᚓ
䛷 ึ 䜑䛶 ᮏ ✀ 䛾౵ ධ 䞉 ᐃ ╔ 䛜 ☜ ㄆ 䛥 䜜䛶 䛔䜛 䛣䛸 䛛䜙
䜛✀䛚䜘䜃⣔⤫䜢᥈⣴ 䛩䜛䛯䜑䛻໭ᾏ㐨䛷䠏✀䛾ዪ⋤
䠄Choi et al. 2012䠅䚸ᑐ㤿䛻䛿㔩ᒣᕷ䛾㤿ᒣ 䜎䛯䛿㔩
⻏䜢᥇㞟䛧䚸◊✲᪋タ䛷㑅ᢤ⫱✀䜢⾜䛳䛯䚹䠏✀䛾୰䛷
ᒣ 䛛䜙≀㈨䛻௜㝶䛧䛶䚸౵ධ䛧䛯ྍ⬟ᛶ䛜㧗䛔䛸⪃䛘
䜶䝌䜸䜸䝬䝹䝝䝘䝞䝏䛜᭱䜒᭷ᮃ䛷䛒䜛䛣䛸䛛䜙䚸ᮏ✀䛾
䜙䜜䛯䚹
ᡂ⇍䛧䛯ᕢ䛛䜙ୖ఩ 20 ᕢ⛬ᗘ䜢 1䡚2 ୡ௦䛻䜟䛯䛳䛶㑅
ᢤ䛧䚸⣔⤫㐀ᡂ䛾䛯䜑䛾ᇶ♏㞟ᅋ䜢సฟ䛧䚸䛥䜙䛻㑇ఏ
Ꮚᆺゎᯒ䛾䛯䜑䛾 DNA 䝬䞊䜹䞊䜢㛤Ⓨ䛧䛯䚹
䠎䠖䝭䝒䝞䝏䛸䝬䝹䝝䝘䝞䝏䛻䛚䛡䜛⫱✀䜈䛾 BLUP ἲ
䛻䜘䜛㑅ᢤ䛾ᑟධ
㻌 BLUP ἲ䛻䜘䜛ண ⫱✀౯䛻ᇶ䛵䛟㑅ᢤ䠄BLUP 㑅ᢤ䠅
䛿䚸ᐙ␆⫱ ✀䛻䛚䛔䛶ᗈ䛟฼⏝䛥䜜䚸⤒ ῭ᙧ㉁䛾㑇ఏ
ⓗᨵⰋ䛻┠ぬ䜎䛧䛔ᡂᯝ䜢ୖ䛢䛶䛝䛯䚹䛧䛛䛧䛺䛜䜙䚸䝝
䝏㢮䛻䛚䛔䛶䛿㑇ఏ䛺䜙䜃䛻⦾Ṫୖ䛾 2 䛴䛾≉ᛶ䚸䛩
䛺䜟䛱༙ಸᩘᛶ䛾ᛶỴ ᐃᵝ ᘧ䛚䜘䜃୍ጔ ከኵ ไ 䛾⦾
Ṫᵝᘧ䛻䜘䛳䛶䚸BLUP 㑅ᢤ䛾㐺⏝䛜௚䛾ᐙ␆䛻ẚ䜉
䛶❧䛱㐜䜜䛶䛔䜛䚹ᮏ◊✲䛷䛿䚸䝝䝏㢮䛻ᅛ᭷䛾㑇ఏ䛺
䜙䜃䛻⦾Ṫୖ䛾≉ᛶ䜢⪃៖䛻ධ䜜䛶䚸䝝䝏㢮䛾⫱✀䛻
෗┿䠊ᑐ㤿䛷ᤕ⋓䛧䛯䝒䝬䜰䜹䝇䝈䝯䝞䝏䛾 2m 䜢㉸䛘䜛
䛚䛡䜛 BLUP ἲ䛾ィ⟬䜰䝹䝂䝸䝈䝮䜢㛤Ⓨ䛧䛯䚹䛥䜙䛻䚸
ᕧ኱ᕢ䠄ᕥ䠅䛸ാ䛝⻏ᡂ⹸䠄ྑ䠅
BLUP 㑅ᢤ䛾䝝䝏㢮䛾⫱✀䜈䛾㐺⏝౛䜢䚸௬᝿ⓗ䛺䝭
䝒䝞䝏㞟ᅋ䜢⏝䛔䛶♧䛧䛯䚹
䠐䠖䝭䝒䝞䝏䛸䝬䝹䝝䝘䝞䝏䛾ᚤ⬊Ꮚ⹸⑕䛾ᾐ₶≧ἣ
䠏䠖౵␎ⓗእ᮶✀䝒䝬䜰䜹䝇䝈䝯䝞䝏䛾Ⓨぢ
䜔䝬䝹䝝䝘䝞䝏䛾䝁䝻䝙䞊䛜Ṛ⁛䛩䜛㔜⠜䛺⑓Ẽ䛷䛒䜛䚹
ᚤ⬊Ꮚ⹸䛾ᐤ⏕䛻䜘䜚Ⓨ⑕䛩䜛䝜䝊䝬⑓䛿䚸䝭䝒䝞䝏
䛣䜜䜎䛷᪥ᮏ䛷䛿䚸እ᮶ᛶ䝇䝈䝯䝞䝏㢮䛾౵ධ䛿☜ㄆ
ᅜෆ䛻⏕ᜥ䛧䛶䛔䜛䝭䝒䝞䝏䛚䜘䜃䝬䝹䝝䝘䝞䝏䛻ᐤ⏕
䛥䜜䛶䛔䛺䛛䛳䛯䛜䚸௒ᅇ㛗ᓮ┴ᑐ㤿䛻䛚䛔䛶᪥ᮏᮍ
䛩䜛ᚤ⬊Ꮚ⹸䛾ᾐ₶≧ἣ䜢 PCR デ᩿ἲ䛻䜘䜚᳨ฟ䛧䚸
グ㘓䛾䝒䝬䜰䜹䝇䝈䝯䝞䝏䛸ㄆ䜑䜙䜜䜛ാ䛝⻏ಶయ䜢ᤕ
䝅䞊䜽䜶䞁䝇ゎᯒ䛻䜘䜚ྠᐃ䜢⾜䛳䛯䚹䝉䜲䝶䜴䝭䝒䝞䝏䚸
䝙䝩䞁䝭䝒䝞䝏䚸䝉䜲䝶䜴䜸䜸䝬䝹䝝䝘䝞䝏䛾 3 ✀䛻䛚䛔
䛶䚸Nosema apis 䛸 N. bombi 䛾ᐤ⏕䛜䛭䜜䛮䜜☜ㄆ䛥
manipulated and unmanipulated individuals revealed that
䜜䛯䚹䝉䜲䝶䜴䜸䜸䝬䝹䝝䝘䝞䝏䛿䚸᥇㞟䛧䛯඲ᆅᇦ䛾
the removal treatment did not have any negative effects
ಶయ䛛䜙 N. bombi 䛜᳨ฟ䛥䜜䛯䚹rRNA 䛾䝅䞊䜽䜶䞁䝇
on female clutch size or egg hatchability for males. In
ゎᯒ䛛䜙䛿䚸ᅜෆ䛷䝭䝒䝞䝏䛻ᐤ⏕䛧䛶䛔䜛 N. apis 䛿䚸
conclusion, stable isotope analysis of the middle leg
⑓ཎᛶ䛾ప䛔⣔⤫䛷䛒䜛䛣䛸䛜♧၀䛥䜜䛯䚹
tarsus of K. deyrolli is useful for estimating its trophic
position without lethal or any negative fitness effects.
㸱㸬Research projects and annual reports
1:
Discovery
(Hymenoptera:
of
a
worker
Vespidae)
of
from
Vespa
velutina
Tsushima
Island,
3: Herbivore community promotes trait evolution in a
leaf beetle via induced plant response.
Several
Japan.
recent
studies
have
emphasised
that
We captured one worker of Vespa velutina on
community composition alters species trait evolution.
Tsushima Island of Nagasaki Prefecture on 20 October
Here, we demonstrate that differences in composition of
2012. This is the first collection record of V. velutina
local herbivore communities lead to divergent trait
from Japan. Since V. velutina is known for its great
evolution of the leaf beetle Plagiodera versicolora
capacity to adapt to environmental changes, it is
through plant-mediated indirect interactions. Our field
suggested that the spread of V. velutina is likely to affect
surveys, genetic analyses and community-manipulation
the unique ecosystem of Tsushima Island in the near
experiments
future.
composition determines the degree of herbivore-induced
show
that
herbivore
community
regrowth of willows (Salicaceae), which in turn,
2: A non-lethal sampling method for estimating the
promotes the divergent evolution of feeding preference
trophic position of an endangered giant water bug
in the leaf beetle from exclusive preference for new
using stable isotope analysis.
leaves to a lack of preference among leaf-age types.
We propose a non-lethal sampling method involving
Regrowth intensity depends both on the differential
stable isotopeanalysis for estimating the trophic position
response of willows to different herbivore species and
Kirkaldyia
the integration of those herbivore species in the
of
the
endangered
giant
water
bug
(=Lethocerus) deyrolli (Heteroptera: Belostomatidae) in
community.
the wild. Kirkaldyia deyrolli individuals were collected
involves phenological changes in new leaf production,
and their d15N and d13C values were measured. The
leaf beetle populations develop divergent feeding
d15N and d13C values of periphyton and particulate
preferences according to local regrowth intensity.
organic matter, the basal food sources in lentic
Therefore, herbivore community composition shapes the
ecosystems of rice fields, were also measured to estimate
selection regime for leaf beetle evolution through
the trophic position of K. deyrolli. When individual
trait-mediated indirect interactions.
Because
herbivore-induced
regrowth
isotopic signatures of the whole body were compared
with those of their middle leg tarsus, we found strong
䠐䠊ㄽᩥ䠈ⴭ᭩䛺䛹
correlations between them for both d15N and d13C. To
Ꮫ ⾡ㄽᩥ
estimate their trophic position without killing individuals,
1. Utsumi S, Ando Y, Roininen H, Takahashi J., Ohgushi T.:
we constructed a regression model incorporating their
middle leg tarsus’s isotopic signatures and their body
Herbivore community promotes trait evolution in a leaf
size as explanatory variables. This non-lethal method
beetle via induced plant response. Ecology Letters. (2013)
revealed that K. deyrolli showed great individual
16, 362- 370.
variation in its d15N which is a proxy of trophic position,
ranging from 5.60&to 8.11&. To evaluate the negative
2. Ohba S, Takahashi J, Okuda N: A non-lethal sampling
effects of our non-lethal method on the fitness of K.
method
deyrolli, we examined how the removal of the middle leg
endangered giant water bug using stable isotope analysis.
tarsus
Insect Conservation and Diversity. (2013) 6, 155-161
affected
reproductive
performance
under
laboratory conditions. A comparison between
the
for
estimating the trophic position
of an
3. ቃⰋᮁ䞉㧗ᶫ⣧୍ 䠖ᑐ㤿䛷Ⓨぢ䞉ᤕ⋓䛥䜜䛯䝒䝬䜰䜹䝇䝈䝯
䝞䝏䠄Vespa velutina)䛾ാ䛝䛻䛻䛴䛔䛶䠊 ᪻⽝䠊༳ๅ୰
7䠊㧗ᶫ⣧୍䠖 䝭䝒䝞䝏䛚䜘䜃䝬䝹䝝䝘䝞䝏䛻䛚䛡䜛⑓ཎᛶᚤ⏕
≀䛾ᾐ₶≧ἣ䛻䛴䛔䛶䠊᪥ᮏ᪻⹸Ꮫ఍➨73ᅇᮐᖠ኱఍䠊
2013ᖺ9᭶16᪥䠊ᮐᖠᕷ
4䠊Kiyoshi T, Fukui M, Fukunaga K, Takahashi J, Tsubaki Y. A
Preliminary Report on the Genetic Diversity of a Highly
Endangered dragonfly, Libellula angelina Selys, 1883, in
the Okegaya-numa Pond, Iwata, Japan. Tombo. Inpress.
8䠊㧗ᶫ⣧୍䠖 DNAᢳฟ䛸PCRᐇ㦂䠊ᓥ᰿┴❧὾⏣㧗➼Ꮫᰯ䠊
2013ᖺ9᭶21᪥䠊὾⏣ᕷ
9䠊㧗ᶫ⣧୍䠖 䝭䝒䝞䝏䛸㣴⻏䠊㣴⻏ᢏ⾡ᣦᑟㅮ⩦఍䠊2013ᖺ9
᭶26᪥䠊ྡྂᒇᕷ
10.㧗ᶫ⣧୍䠖 䝭䝒䝞䝏⑓ཎᛶᚤ⏕≀䛾ᾐ₶≧ἣ䠊⇃ᮏ┴㣴⻏
༠఍䠊2013ᖺ10᭶7᪥䠊⇃ᮏᕷ
ⴭ᭩
1䠊䜏䛴䜀䛱༠㆟఍⦅䠖 㣴⻏ᐙྥ䛡䟿㣴⻏䝬䝙䝳䜰䝹III䠊ዪ⋤
⻏䛾స䜚᪉䠊䠄2013䠅ᮾி䠊pp99. http://www.beekeeping.or.jp/
11䠊㧗ᶫ⣧୍䠖 䝭䝒䝞䝏䛸㣴⻏䠊㣴⻏ᢏ⾡ᣦᑟㅮ⩦఍䠊2013ᖺ
10᭶10᪥䠊⇃ᮏᕷ
12䠊㧗ᶫ⣧୍䞉㧗ᶫ⛸୍䞉ᒾཱྀ೺ኴ㑻䞉㔛ぢඃ䞉ཎ⏣䝺䜸䝘䞉ቃ
Ⰻᮁ䞉ᒣᮧ㎮⨾䠖ᑐ㤿䛻䛚䛡䜛እ᮶✀䝒䝬䜰䜹䝇䝈䝯䝞䝏䛾ᖐ
໬䛸⿕ᐖ䛻䛴䛔䛶䠊➨68ᅇ᪥ᮏ⾨⏕ື≀Ꮫ఍す᪥ᮏᨭ㒊౛
⣖せ
1䠊ᒸ⏣኱ᆅ䞉㮚㔝⏤㔛Ꮚ䞉⏣୰⨾Ꮚ䞉బ䚻ᮌ୍㤿䞉Ჴᶫ㟹⾜䞉
㧗ᶫ⣧୍䞉బ಴ṇ᫂䞉➉ෆᐇ䠖 ᪥ᮏᅜ⏘䝝䝏䝭䝒䛾䜘䜛⫵⬊
䝬䜽䝻䝣䜯䞊䝆䛾ච␿ᶵ⬟䛻ཬ䜌䛩ᙳ㡪䠊 ி㒔⏘ᴗ኱Ꮫඛ
➃⛉Ꮫᢏ⾡◊✲ᡤᡤሗ 䠊(2013) 12, 33-44
2䠊㔝ᮧဴ㑻䞉㧗ᶫ⣧୍䞉➉ෆ๛䠖 䝝䝏㢮䛾⫱✀䜈䛾BLUPἲ
䛻䜘䜛㑅ᢤ䛾ᑟධ䠊 ி㒔⏘ᴗ኱Ꮫඛ➃⛉Ꮫᢏ⾡◊✲ᡤᡤ
ሗ 䠊(2013) 12, 45-57
3䠊㧗ᶫ⣧୍䞉➉ෆᐇ䞉ᯇኼ⪔୕䞉㔝ᮧဴ㑻䠖 䝭䝒䝞䝏䛚䜘䜃䝬
䝹䝝䝘䝞䝏䛻䛚䛡䜛ᚤ⬊Ꮚ⹸䛾ᾐ₶≧ἣ䠊 ி㒔⏘ᴗ኱Ꮫඛ
➃⛉Ꮫᢏ⾡◊✲ᡤᡤሗ 䠊(2013) 12, 59-68
4䠊୰ᮧ⣧䞉ᮌᮧ⃈䞉㧗ᶫ⣧୍䞉బ䚻ᮌṇᕫ䞉┾㘠᪼䠖 䝛䜸䝙䝁
䝏䝜䜲䝗䛻㛵䛩䜛ᒣ⏣ㄽᩥ䛾ၥ㢟Ⅼ䛻䛴䛔䛶䠊 ⌧௦໬Ꮫ 䠊༳
ๅ୰䠊
5䠊㧗ᶫ⣧୍䠖 ᪥ᮏ䛻䛚䛡䜛䝭䝒䝞䝏䛾ῶᑡཎᅉ䛻䛴䛔䛶̺ᮏ
ᙜ䛻䝭䝒䝞䝏䛯䛱䛿ᾘ䛘䛯䛾䛛̺䝭䝒䝞䝏୙㊊䠊 ⎔ቃ䛸೺ᗣ 䠊
༳ๅ୰䠊
䠑䠊Ꮫ఍Ⓨ⾲䛺䛹
1䠊㧗ᶫ⣧୍: 䝭䝒䝞䝏◊✲䛾᭱๓⥺̺♫఍ᛶ᪻⹸䛾୙ᛮ㆟䜢
᥈䜛̺䠊බ┈㈈ᅋἲேయ㉁◊✲఍䠊2013ᖺ4᭶20᪥䠊ி㒔ᕷ
2䠊㧗ᶫ⣧୍䠖 ➨2ᅇ㣴⻏䛾䛩䛩䜑䠊ி㒔⏘ᴗ኱Ꮫᩍ㣴ㅮᗙ䠄๓
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9᭶5᪥䠊ᮐᖠᕷ
఍䠊2013ᖺ10᭶26᪥䠊⚟஭ᕷ
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ᕷ
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㤿䝙䝩䞁䝭䝒䝞䝏㒊఍䠊2013ᖺ12᭶20᪥䠊ᑐ㤿ᕷ
䠒䠊䛭䛾௚≉グ஦㡯
䠍䠅㻌 እ㒊㈨㔠
1䠊⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ⱝᡭ䠄B䠅
ㄢ㢟ྡ䠖่䛥䛺䛔䝭䝒䝞䝏䛾㑇ఏᏛⓗゎᯒ
◊✲௦⾲⪅䠖㧗ᶫ⣧୍, ྲྀᚓᖺᗘ䠖H24-25 ᖺ (2 ᖺ)
2䠊⎔ቃ┬⎔ቃ⥲ྜ◊✲᥎㐍㈝䞉ⱝᡭ
ㄢ 㢟ྡ 䠖ᅾ᮶ 䝬䝹䝝䝘䝞䝏䛻䜘䜛⎔ ቃㄪ ࿴ ᆺ䝫䝸䝛䞊䝅䝵䞁
ᵝᘧ䛾☜❧䛻㛵䛩䜛◊✲
◊✲௦⾲⪅䠖㧗ᶫ⣧୍, ྲྀᚓᖺᗘ䠖H24-26 ᖺ (3 ᖺ)
3䠊⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ᇶ┙◊✲䠄B䠅
ㄢ 㢟ྡ 䠖ᒁ ᡤⓗ ㏆ ⦕ ✀䛾⏕ ᜥ ᆅศ 㞳 䛸ᙧ ㉁⨨ ᥮ 䜢䜒䛯䜙䛩
⏕ែᏛⓗせᅉ
◊✲ศᢸ⪅䠖㧗ᶫ⣧୍, ྲྀᚓᖺᗘ䠖H23-25 ᖺ (3 ᖺ)
4䠊⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ᇶ┙◊✲䠄B䠅
ㄢ 㢟ྡ 䠖ᅾ᮶ 䝬䝹䝝䝘䝞䝏䛻䜘䜛⎔ ቃㄪ ࿴ ᆺ䝫䝸䝛䞊䝅䝵䞁
ᵝᘧ䛾☜❧䛻㛵䛩䜛◊✲
◊✲ศᢸ⪅䠖㧗ᶫ⣧୍, ྲྀᚓᖺᗘ䠖H24-26 ᖺ (3 ᖺ)
5䠊⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ᇶ┙◊✲䠄B䠅
ㄢ㢟 ྡ䠖ཎ ጞⓗ ┿♫ ఍ ᛶ✀ 䛾⦾ Ṫไ ᚚ䠖㑇 ఏᏊ 䛛䜙⾜ື䜎
䛷
◊✲ศᢸ⪅䠖㧗ᶫ⣧୍, ྲྀᚓᖺᗘ䠖H24-26 ᖺ (3 ᖺ)
6䠊ጤク◊✲䞉♫ᅋἲே᪥ᮏ㣴⻏䛿䛱䜏䛴༠఍
➨ 1 ᅇ⏕࿨㈨※⎔ቃᏛ⛉༞ᴗ◊✲Ⓨ⾲఍
䝫䝇䝍䞊Ⓨ⾲ඃ⚽㈹㻌 ୰ℊዌ⤮㻌 2014 ᖺ 2 ᭶ 28 ᪥
◊✲ศᢸ⪅䠖㧗ᶫ⣧୍, ྲྀᚓᖺᗘ䠖H25-26 ᖺ (2 ᖺ)
7䠊ጤク◊✲䞉♫ᅋἲே᪥ᮏ䝻䞊䝲䝹䝊䝸䞊ᰯṇྲྀᘬ༠㆟఍
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8䠊ጤク◊✲䞉ᰴᘧ఍♫䝇䝆䝵䞁䞉䝆䝱䝟䞁
◊✲ศᢸ⪅䠖㧗ᶫ⣧୍, ྲྀᚓᖺᗘ䠖H25-26 ᖺ (2 ᖺ)
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䠏䠅㻌 䛭䛾௚
䝯䝕䜱䜰
1䠊ᮅ᪥᪂⪺䠖2013 ᖺ 1 ᭶ 14 ᪥
2䠊ᅜ❧⎔ቃ◊✲ᡤ䞉⎔ቃᒎᮃྎ䠖
䐣
http://tenbou.nies.go.jp/news/jnews/detail.php?i=10085
䐤
3䠊䝬䜲䝘䝡䞉䝙䝳䞊䝇䠖
http://news.mynavi.jp/news/2012/12/27/126/index.html
4䠊yahoo 䝙䝳䞊䝇䠄䝬䜲䝘䝡䞉䝙䝳䞊䝇䛾㌿㍕䠅䠖
http://headlines.yahoo.co.jp/hl?a=20121227-00000058-myc
omj-sci
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8䠊ㄞ኎᪂⪺䠖2013 ᖺ 9 ᭶ 16 ᪥
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9䠊ㄞ኎᪂⪺䠖2013 ᖺ 9 ᭶ 19 ᪥
䝻䝇䝈䝯䝞䝏䛾ᕢ䛾ㄪᰝ䠄2 ᮇ⏕ཎ⏣䝺䜸䝘䠅, 䐦➨ 1 ᐇ㦂ᐊᲷ
10䠊す᪥ᮏ᪂⪺䠖2013 ᖺ 9 ᭶ 19 ᪥
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11䠊ி㒔୕᮲䝷䝆䜸䜹䝣䜵䠖2013 ᖺ 9 ᭶ 29 ᪥ᨺ㏦䠖䝀䝇䝖ฟ₇
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13䠊ㄞ኎᪂⪺䠖2013 ᖺ 10 ᭶ 5 ᪥
14䠊NHK ⥲ྜ㻌 㻌 䛚䛿䜘䛖᪥ᮏ䛄䝭䝒䝞䝏䜢く䛖እ᮶✀䝇䝈䝯䝞
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http://cgi4.nhk.or.jp/eco-channel/jp/movie/play.cgi?did=D
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Laboratory of Protein Structural Biology
Prof. Hideaki Tsuge, Ph.D
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Assit. Prof. Toshiharu Tsurumura
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3. Research projects and annual reports
4. -(98
We have been focusing our research on the structural biology of
E Tsurumura T, Qiu H. Tsumori Y, Oda M, Nagahama M, Sakurai J,
infectious disease. Especially our target is macromolecular complex
Tsuge H
and we would like to reveal the interaction between the infectious
Arginine ADP-ribosylation mechanism based on structural
factor protein and human protein.
snapshots
of iota-toxin and actin complex.
Proc Natl Acad Sci U.S.A. 110(11):4267-4272. (2013)4
(1) Actin ADP-ribosylating toxin (ADPRT) such as iota toxin from
E Tsurumura T, Qiu H, Yoshida T, Tsumori Y, Hatakeyama D,
C.perfringens ADP-ribosylates Arg-177 of α-Actin, inhibits actin
Kuzuhara T, Tsuge H.
polymerization and induce cell rounding. Recently we resolved the
first crystal structure of Ia in complex with actin
and the
Conformational Polymorphism of m(7)GTP in Crystal Structure of
the PB2 Middle Domain from Human Influenza A Virus
non-hydrolyzable NAD+ analog βTAD; however, the structures of the
PLoS One. 8(11):e82020 (2013)
NAD+ bound form (NAD+-Ia-actin) and the ADP-ribosylated form
E Tsuge H and Tsurumura T
(Ia-ADP-ribosylated (ADPR)-actin) remain uncertain. We found that
ethylene glycol as cryo-protectant inhibits ADP-ribosylation and then
successfully captured NAD+-Ia-actin in crystal. We revealed
Crystal structure analysis of ADP-ribosylating enzyme and substrate
protein complex
Photon Factory Activity Report4 2012 #30 (2013)
high-resolution structures of NAD+-Ia-actin and Ia-ADPR-actin
obtained by soaking apo-Ia-actin crystal with NAD+ under different
+
J. #)98
conditions. The structures of NAD -Ia-actin and Ia-ADPR-actin
E ±e
respectively represent the pre- and post-reaction states.
Considering
ĝŁĶĞĔĹàĆîñѨ²<þf2013á
all the structures in each reaction step including βTAD-Ia-actin as a
’#²ďíĊý‹»ðČôĆþǔ†<
transition state, the strain-alleviation model of ADP-ribosylation,
dl¨²<Û 2013.3.19Û ńZKÁ„Ņ
which we proposed previously, is experimentally confirmed and
Mã›X¦§}Åȶ
§Pɔ
improved. Moreover, this reaction mechanism appears to be
Ia-actinÎiV¿–w&ADPJD4Kb
Ž
applicable not only to Ia but also to other ADP-ribosyltransferases.
¹13r“™Ë±Ø·|UƒU%)‘bUáäâgå
(2) Influenza pandemics with human-to-human transmission of the
2013.6.12-14
virus are of great public concern. It is now recognized that a number
MToshiharu TsurumuraHideaki Tsuge
of factors are necessary for human transmission and virulence,
Substrate Selectivity of Monoacylglycerol Lipase based on the
including several key mutations within the PB2 subunit of
Crystal Structure
RNA-dependent RNA polymerase. The structure of the middle
Structural Life Science 7th International Conference on Structural
7
domain in PB2 has been revealed with or without m GTP, thus the
GenomicsR«BI3C:Kš‚äš‚å2013.7.29-8.1
middle domain is considered to be novel target for structure-based
E§Pɔ
drug design. Here we report the crystal structure of the middle domain
ATPase,GTPase(¡²½Ê£¼#&Â҇Yà
of H1N1 PB2 with or without m7GTP at 1.7 and 2.0 resolution
­©|
(Figure B), respectively, which has two mutations (P453H, I471T) to
“™z{x|¬|6F<N“™z{x|äœRå2013.10.2
increase electrostatic potential and solubility. Here we report the
ńZKÁ„Ņ
7
m GTP has unique conformation differ from the reported structure.
M¤›•yj®‰§Pɔ
7-methyl-guanine is fixed in the pocket, but particularly significant
]ÑÆ¥~&CChalfRZ
change is seen in ribose and tri-phosphate region: the buried
“™¿–|U¨™x|䨙å2013.10.12
7-methyl-guanine indeed binds in the pocket forming by H357, F404,
Mã›X¦¶
j®‰§}ÅȧPɔ
7
ÝW‹
ŸÚ
Ã
E361 and K376 but other region of m GTP continues directed to the
,LAK.L3-+K5 RNA EJGIN7 CAP ¿i
outer domain (Figure B, C). The presented conformation of m7GTP
ŸÚ
may be a clue for the anti-influenza drug-design.
@8FLB´¸c×Ulh€-,L2älh€å
(3) We are currently going on the structural study of poly-ADP-ribose
2013.11.2
glycohydrolase, chaperone of Aeromonas sobria serineproteiase, and
novel peroxidase DyP.
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dl<µ\°Û 0Yǔ†£ 169 :/Û :/
ĮĢĸŁ B ¡:/Û :/
Journal of Crystallography (Hindawi) Editorial board
Advances in Biology (Hindawi) Editorial board
(4) (Ť
üï
(5) óþ
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CABD?F7GIIH
Prof. Toru Terachi, Dr. Agr. Ɗ
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Assist. Prof. Kiyoshi Takahashi, Dr. Sci.
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džǗǂĀ LJǫǏƹů ŭ đ Þ k ǖ „ ǚÆ W ǖǃǪȇȔǿ
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D ý Ĉ Ǯj ¯ ljƸÆ W ¯ Ń Ǯ
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ð ljǏǩȩȕȦǿȞǻȪƸ
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ȨǖǰǸȈȣȜ?ǟ ƚƲƩƊƧƮƯƵƬ JĆǮÆWljǕǥǨƽƸ
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WȇȔǿǜŖĜĆǖÈç,dîçeǜȠȌȣÈçǗǙ
Ɗ
ǪșȦȀȝǰȏȇȔǿǗƸȤȇȄǚǓƽǕƸ]ÈæǜWƃ
Research projects and annual reports
ǁǨƸ),9ǜÆWǗ¥ĆǢǖƸȡDzȗȀDzǼȣǮg
We have performed the following three major research
ĖLJnjǪȂȄȋȞǮgšLJnjǏƹǍǜǖƸdžǫǨ Ɩ Ćǜ
projects relating to the organellar genomes in higher
ÈçǮqōǚƸĴěǜŠdĕ¨ƿjƆǮj¯ljǏƹ
plants:
ǍǜĖÃƸȕȦǿȞǻǗȍȜȍǚǓƽǕǝĕ¨ƿǂ‘Ǩ
1: Production of transplastomic plants that are useful for
ǫǙǁǒǏǥǜǜƸșȦȀȝǰȏȇȔǿǚǓƽǕǝ ?
human beings.
ǟ ŠdƸȤȇȄǚǓƽǕǝȗǴȢȉȦŠdǮĴ
2: Comprehensive studies on the molecular mechanism
ěǾȒȞǚ¢Ǔĕ¨ƿǮ‘ǪdžǗǂǖǃǏȩR ƓȪƹƊ
of the male-sterility/fertility restoration system in radish.
3: Comparative mitochondrial genome analysis of
Triticum and Aegilops using alloplasmic lines of
common wheat.
The
first
project
aims
at
producing
various
transplastomic plants that will be useful for human
beings.
Currently
several
transplastomic
lines
(containing genes like apx, ferritin, etc...) have been
produced
using
tobacco
as
a
model
plant
and
R ƓƐƊ ĴěǾȒȞǚȈDzȅǜȗǴȢȉȦŠdǂr$LJ
experiments producing transplastomic crops such as
ǫǏĕ¨ƿȤȇȄ
tomato, wheat and lettuce have been conducted.
yȯŨîVȩƠƯƱƭƊƪƳƲƶƱȪƸƸAȯĕ¨ƿƊ
The second project tries to reveal interaction between
èǚȤȇȄǜYCƸ‘ǨǫǏ Ʀ ƒ ǝȬǜǣǖƼǒǏǂƸ
mitochondrial
džǫǮÔ Ħ Æ W ǖŰ į Ė j NJǪǢǖħ ǕǪdžǗǂǖǃƸ
male-sterility and fertility restoration system found in
ÏȩƦ Ɠ ȪǜĆdǮ_ũǚ‘ǪdžǗǂǖǃǏƹƦ Ɠ Ǯðƽ
radish.
ǏjƆǖƸƦ ƒ ǚr$LJǫǏȗǴȢȉȦŠdǂÐþǚ
and nuclear Rf genes have been examined to reveal
¢LJǫǕǀǩƸŔ*ƸĢńLJǫǕƽǪdžǗǂĀLJǫǏƹǢǏ
evolutionary aspect of the system.
Ĵǜū,ǂŨîVǗÓǡǕȭǚǙǒǕƽǪdžǗǥǭǁǒ
The third project concerns the mitochondrial genome of
ǏƹȤȇȄǝ¸ðçőîïđǜþĉǚaţCǙ¾¬ǖ
Triticum and Aegilops species.
ƼǩƸǍǫĬ œ ƸĴ ç Ũ IJ ǜÎ Ī — F ǜj Ņ j Ɔ ǚ
mitochondrial genome of some species in the genera
ð ǖǃǪǜǖƸ  ǜj Ɔ ǜś s ǂ_ ƽǚº Ž LJǫ
influences on the phenotype of alloplasmic lines of
ǪƹƊ
common wheat.
łȮȪǜȘȥȃǴǼȍǚǓƽǕǝƸ³ǚ‡ǃĚǃ
and
nuclear
genomes
using
a
Genetic variations in both mitochondrial orf138
gene(s)
It is known that the
In order to reveal a mitochondrial
responsible
for
the
phenotypic
difference
ƎƊ ƎƊ ƎƊ
between alloplasmic and euplasmic lines of common
ƎƊ ?ǟ ǜēĩőǮ¢ǓШǿ
wheat, their complete mitochondrial genome sequences
Ȟǻ Ƙ đĘǚǓƽǕƸǾȒȞŀŇǮśǤǕƽǪƹdžǜƾǑƸ
have
Ƹ ?ǟ ǜ ƕ Ćǚ
sequencer.
ǓƽǕǝƸÏȂȨǼǵȦȂȦǽǚǧǪȌȨȇ@‘Ƹ
been
determined
using
the
next-generation
;8754
_û ™Ŏ , pU ”: ǽȣȇȝȦŦ īÔĒťĒŠd (gdh1)
ǮĴěǾȒȞǚ¢Ǔĕ¨ƿȇȔǿǜè“ǔDž. Ċ 124
M. Tsujimura, N. Mori, H. Yamagishi, T. Terachi: A possible
O±½ħĆeŋáȫƉ#x{ȫ2013.10.12-13
breakage of linkage disequilibrium between mitochondrial and
chloroplast genomes during Emmer and Dinkel wheat evolution.
ì˜d, È¿ Ƅĝ, pU ”: ȗǴȢȉȦǮĴěǖƇ
ôëNJǪŠdĕ¨ƿȤȇȄǜŀÁ. Ċ 124 O±½ħ
Genome 56(4), 187-193
ĆeŋáȫƉ#x{ȫ2013.10.12-13
M. Yoshimi, Y. Kitamura, S. Isshiki, T. Saito, K. Yasumoto, T.
Terachi, H. Yamagishi: Variations in the structure and
È¿ Ƅĝ, ŕ ź
,  Ýſ, u½ ĺĎ, pU ”: Ȅȍȥ
transcription of the mitochondrial atp and cox genes in wild
ȜV APX ǮĴěǖ‰ôëNJǪĕ¨ƿȇȔǿǜđĘǖĿ
Solanum species that induce male sterility in eggplant (S.
nLJǫǏ«$ǩǚŲNJǪýĈ. Ċ 124 O±½ħĆeŋá
ȫƉ#x{ȫ2013.10.12-13
melongena). Theor. Appl. Genet.
DOI:10.1007/s00122-013-2097-6
vŢ úˆ, ñ ġĶ, uw <, pU ”: ÏȂȨǼǵ
Ɗ
ȦȀȨǮð ƽǏȈDzǿȦǜȝȍǿȦȎȢǰǾȒȞǜŤ . ŀ Á 3:
<854Ɗ
żŮȈDzǿȦǜ%ȝȍǿȦȎȢǰǾȒȞŤ.ǜÖi. Ċ 124 O
±½ħĆeŋáȫƉ#x{ȫ2013.10.12-13
Y. P. Gyawali, T. Terachi: Mitochondrial genome comparison of
wheat alloplasmic lines by next-generation sequencing. The 8th
ŕ¿ úĸ, Ç øÌ, uw <, pU ”: ÅǾȒȞɚǚǧǩ
International Conference for Plant Mitochondrial Biology
ŞƽǮĀNJ Emmer-Dinkel ǿȞǻǜȝȍǿȦȎȢǰǜ^V. Ċ
ICPMB 2013ȫRosario, Argentina, 2013.5.12-16
124 O±½ħĆeŋáȫƉ#x{ȫ2013.10.12-13
M. Tsujimura, H. Yamagishi, T. Terachi: Mitochondrial genome
Ɗ
analysis of Triticum and Aegilops species relevant to polyploid
=836
wheat evolution. The 8th International Conference for Plant
ȬȪƊ ]ŢŐŪ
Mitochondrial Biology ICPMB 2013ȫRosario, Argentina,
ĂeýĈŏĻ6Ūȧ£›õijİýĈƊ
ňƁEȯĴěǜŠdĕ¨ƿǚǧǪȄȍȤȄĥ—ȕȦǿȞǻ
2013.5.12-16
Gyawali Yadav Prasad, pU ”: Complete sequence of
ǜħšƊ
ýĈĹĤȯpUƊ ”ƎƊ @‘„ȯƟƔƖƏƔƘ Ɗ ƌƕ ƍƊ
mitochondrial genome of an alloplasmic line of common wheat
with Aegilops geniculata cytoplasm. Ċ123O±½ħĆeŋ
vu_eƊ ŐàÈçĂeýĈœƊ &DýĈƊ
áȫñŌ:ȫ2013.3.27-28
ňƁEȯĴěǜŠdĕ¨ƿžķǮ/ðljǏȄȍȤȄĥ—
f½ ´`, Ƈ» hÌ, p( Į€, pU ”: ǷǽȡVŹ—
ÈçǜħšƊ
ąȈDzǿȦǜą—O ’ǚŲǭǪ Rft Šd…ǜÉŘŀÁ.
Ċ123O±½ħĆeŋáȫñŌ:ȫ2013.3.27-28
ýĈĹĤȯpUƊ ”ƎƊ @‘„ȯƟƔƖƏƔƗ Ɗ ƌƔ ƍƊ
ƈ@_eƊ åUýĈȆȦȇȨƊ &DýĈƊ
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ňƁEȯĴěǜ‹őŔ¨žķǮðƽǏȄȍȤȄĥ—ǿȞǻ
ǜ+Ɗ
ÈçǜȝȍǿȦȎȢǰǾȒȞǜŀÁ 2. Aegilops speltoides ǜē
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ĩőǮ¢ǓШđĘǜȝȍǿȦȎȢǰǾȒȞ. Ċ123O±½ħĆ
eŋáȫñŌ:ȫ2013.3.27-28
ČØ_eƊ ŠdjƆȆȦȇȨƊ ‹őŔ¨ÈçȌȁDzȦ ãƊ
&DýĈňƁEȯȜDzǼȥȍȞǮðƽǏȍȜȍǜĴě‹őŔ
āÕ ²±ğ, ŕ¿ ¹Œ, È¿ Ƅĝ, pU ”: ĴěǜŠ
¨žķǜþĉƊ
dĕ¨ƿǮðƽǏƇâ„ǽȣȇȉǷȦG¸Èçǜħš. Ċ
ýĈĹĤȯpUƊ ”ƎƊ @‘„ȯƟƔƗ Ɗ ƌƓ ƍƊ
123O±½ħĆeŋáȫñŌ:ȫ2013.3.27-28
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ȭȪƊ ǍǜƊ Ɗ
ǮĴěǾȒȞǚ¢Ǔĕ¨ƿȤȇȄǜ+. Ċ123O±½ħĆ
±½eķ¤ĭƊ ĂýŏoÄbKȩpUȪƊ
eŋáȫñŌ:ȫ2013.3.27-28
ƞƬƱƬƊƋƊƞƬƱƬƵƯƪƊƥƷƴƵƬưƴƊƬƫƯƵƲƳȩpUƸƇÍȪƊ
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ĴěǾȒȞǚ¢Ǔĕ¨ƿȇȔǿǜ+. Ċ123O±½ħĆ
ƚƳƬƬƫƯƱƭƊƥƪƯƬƱƪƬƊƬƫƯƵƲƳȩpUȪƊ
_eŋ}ȯţƒĉ_e_eŴƺÈçȔDzǷȋǼȒȥȃȨè
ŊƻȩpUȪƸČØ_eîIíZeĠîçeƂƺìŊŻQŠ
eŋáȫñŌ:ȫ2013.3.27-28
eƻȩƇÍȪƊ
āÕ ²±ğ, È¿ Ƅĝ, pU ”: ĴěǜŠdĕ¨ƿ
ǚǧǩ + LJǫǏǽȣȇȉǷȦƇ G ¸ ȇȔǿǜè “ ǔDž. Ċ
Ɗ
124 O±½ħĆeŋáȫƉ#x{ȫ2013.10.12-13
Ɗ
教授 野村哲郎
動物遺伝育種学研究室
Prof. Tetsuro Nomura, Ph. D.
Laboratory of Animal Genetics and Breeding
１．研究概要
生物集団内に保有される遺伝的多様性は、進化や動
系統に割り振るものである。方法の有効性を、実際の黒
毛和種の血統および SNP 情報を用いて検証した。
植物の品種改良（育種）にとって不可欠な素材である。
たとえば、生物種が様々な環境に適応し進化していくた
２）ミツバチおよびマルハナバチの育種へのＢＬＵP 法に
めには、それぞれの環境に適した多様な遺伝子が集団
よる選抜の導入
内に存在する必要がある。また、動植物の育種において
BLUP 法による予測育種価に基づく選抜（BLUP 選抜）
も、育種家が改良しようとする集団内に保有される遺伝
は、家 畜育 種 において広く利 用され、経 済 形質 の遺 伝
的多様性に働きかけ、望ましい遺伝子を人為選択によっ
的改良に目覚ましい成果を上げてきた。しかしながら、ハ
て集積することが基本となる。
チ類においては遺伝ならびに繁殖上の２つの特性、すな
動物遺伝育種学研究室では、動物集団の遺伝的多様
わち半倍数性の性決定様式および一妻多夫制の繁殖
性の維持と利用について、保全遺伝学および育種学の
様式によって、BLUP 選抜の適用が他の家畜に比べて
観点から研 究 を進めている。具体的には、つぎのような
立ち遅れている。そこで、ハチ類に固有の遺伝ならびに
研究テーマで研究を展開している。
繁殖上の特性を考慮に入れて、ハチ類の育種における
１）動物集団の遺伝的多様性の評価方法の開発
BLUP 法の計算アルゴリズムを開発した。さらに、BLUP
野生動物や家畜について血統記録や DNA 情報を
用いて集団内の遺伝的多様性を評価するための方法
選抜のハチ類の育種への適用例を、仮想的なミツバチ
集団を用いて示した。
について、理論的研究を行っている。
２）絶滅が危惧される野生動物の維持集団および家畜希
少系統における遺伝的多様性の維持方法の確立
３．Research projects and annual reports
Genetic diversity retained in populations is an essential
動物園や自然公園などで動物を維持するときに、ど
material for adaptive evolution and breeding of plants
のような個体を親として残し、どのような交配を採用す
and animals; species can adapt through natural selection
れば遺伝的多様性が効率的に維持できるかについて
to changing environment, if they have sufficient genetic
研究を進めている。
diversity.
３）動物および昆虫集団における遺伝的多様性の調査
日本で普通に見られるナミテントウやその近縁 種 の
Breeders of domesticated plants and animals
can genetically improve their materials by artificial
selection on genetic variability.
Our laboratory is
鞘翅斑紋を支配する遺伝子の地理的分布に関する調
researching the methodology for evaluation, maintenance
査、家畜の血統記録を用いた遺伝的多様性の調査を
and utilization of genetic diversity in wild and
行っている。
domesticated animal populations.
Our main research
projects and the annual reports are as following:
２．本年度の研究成果
１）血統および DNA 情報を用いた黒毛和種の系統再
構築法の開発
黒毛和種においては、少数の人気種雄牛に繁殖供用
1: Development of method for re-establishing strains in
the Japanese Black cattle population, using pedigree and
DNA information
が集中することによって、品種内の遺伝的多様性が激減
In the Japanese Black cattle population, intensive use
していることが指摘されている。遺伝的多様性を維持・回
of popular sires for reproduction has led to a drastic
復させるためには、品種内 に遺伝的に分 化した系 統 を
decline of genetic diversity within the breed.
再構築することが有効であると言われている。そこで、血
been
統および SNP 情報を用いて品種内に系統を再構築する
divergent
ための手法を開発した。開発した手法は、まず血統情報
maintaining the genetic diversity in the Japanese Black
に基づいて各系統のコアとなる個体群を設定し、新たな
cattle.
候補個体は SNP 情報を用いた判別分析によって適切な
in the breed, using pedigree and SNP information.
proven
that
strains
re-establishment
is
effective
for
of
It has
genetically
recovering
and
We developed a method for establishing strains
In
the method, animals representative of a strain are first
selected as a ‘core’ group of the strain.
Assignment of
農林水産省独立行政法人評価委員会委員
a candidate animal to the group is judged by a
全国和牛登録協会
discriminant
Asian-Australasian Journal of Animal Sciences, editor
function
with
SNP
markers.
The
effectiveness was verified with actual pedigree and SNP
育種推進委員
３） その他
なし
data of the Japanese Black cattle.
2: Application of BLUP selection to honeybee and
bumblebee breeding
Selection on predicted breeding values by BLUP
methodology
(BLUP
selection)
has
been
widely
practiced in animal breeding, leading to a remarkable
genetic improvement in economic traits.
However, the
application of BLUP selection to bee breeding has not
been as advanced as in other agricultural species due to
two distinctive genetic and reproductive peculiarities in
bees,
i.e.,
polyandrous
haplodiploid
breeding
sex
determination
system.
Taking
the
and
two
peculiarities into account, we developed a computing
algorithm for BLUP in bee breeding.
Application of
BLUP selection was illustrated with a hypothetical honey
bee population.
４．論文，著書など
野 村 哲 郎 ・ 高 橋 俊 一 ・ 竹 内 剛 (2013). ハ チ 類 の 育 種 へ の
BLUP 法による選抜の導入．京都産業大学先端科学技術研
究所所報. 第 12 号. 45-57.
高橋純一・竹内 実・松本耕三・野村哲郎 (2013). ミツバチお
よびマルハナバチにおける微胞子虫の浸潤調査. 京都産業
大学先端科学技術研究所所報. 第 12 号. 59-67.
野村哲郎（2013）．遺伝的多様性の確保． 牛疫学（第 3 版）
近代出版．
野村哲郎（2013）, 牛の育種
牛の科学
pp.141-159. 朝倉
書店.
５．学会発表など
野村哲郎（2013）京都産業大学ミツバチ産業科学研究セン
ターの概要. 第25回ミツバチ科学研究会. 玉川大学．
2013.1.13.
６．その他特記事項
１） 外部資金
科学研究費補助金 基盤研究（B）
課題名：選抜育種による北海道産マルハナバチの高受粉系
統の作出
研究代表者：野村哲郎, 取得年度：H24-26 年 (3 年)
２） 学外活動
食料・農業・農村政策審議会委員
ハウス栽培の受粉用昆として導入され、北海道で分布域を
拡大している外来種のセイヨウオオマルハナバチ（左）と
セ イ ヨ ウ オ オマ ル ハ ナ バ チに 代 わ る 新 たな 受 粉 昆 虫 と し
て注目される在来種のエゾオオマルハナバチ(右)
選 抜 育 種 に より エ ゾ オ オ マル ハ ナ バ チ の高 受 粉 能 力 系 統
の作出を目指しています。
෸ᩍᤵ㻌 ᮏᶫ㻌 ೺
᳜≀⏕⌮Ꮫ◊✲ᐊ
Assoc. Prof. Ken MOTOHASHI, Ph. D.㻌
㻸㼍㼎㼛㼞㼍㼠㼛㼞㼥㻌㼛㼒㻌㻼㼘㼍㼚㼠㻌㻼㼔㼥㼟㼕㼛㼘㼛㼓㼥㻌㼍㼚㼐㻌㻮㼕㼛㼏㼔㼑㼙㼕㼟㼠㼞㼥㻌
ຓᩍ㻌 ᱩᕝ㻌 ཭Ꮨ㻌
Assist. Prof. Yuki OKEGAWA, Ph. D.
䠍䠊◊✲ᴫせ㻌
䛻䛚䛔䛶ᶵ⬟ 䛧䛶䛔䜛䚹䛣䜜䜙䛾ᵓ㐀䛾␗䛺䜛ከ䛟䛾ᶆ
᳜≀⏕⌮Ꮫ◊✲ᐊ䛷䛿䚸᳜≀ⴥ⥳య䛻䛚䛡䜛ᶵ⬟ไ
ⓗ䝍䞁䝟䜽㉁䜢䚸䝏䜸䝺䝗䜻䝅䞁䛿䛹䛾䜘䛖䛻ぢศ䛡䚸ⴥ
ᚚ䛻⯆࿡䜢ᣢ䛱䚸኱䛝䛺䝔䞊䝬タᐃ䜢⾜䛳䛶䛔䜛䚹㻌
⥳యෆ䛷ΰ஘䛩䜛䛣䛸䛺䛟┦ ᡭ䝍䞁䝟䜽㉁ 䜢ㄆ㆑ 䛧䚸ᚲ
᳜≀䛾኱ 䛝䛺≉ᚩ 䛾䜂䛸䛴䛻ගྜᡂ䛜䛒䜛䚹㧗➼᳜
せ䛺㑏ඖຊ䠄䛴䜎䜚㟁Ꮚ䠅䜢౪⤥䛧䛶䛔䜛䛾䛛䚸᫂䜙䛛䛻
≀䛾ගྜᡂ䛿ⴥ⥳య䛸࿧䜀䜜䜛」ᩘ䛾⭷⣔䛛䜙䛺䜛ᙧ
䛩䜛䚹䜎䛯䚸ⴥ⥳య୰䛻」ᩘ䛾䜰䜲䝋䝣䜷䞊䝮䜢ᣢ䛴䝏䜸
ែⓗ䛻䜒」㞧䛺䜸䝹䜺䝛䝷䛷㐍⾜䛧䚸㻯㻻㻞 ᅛᐃ䛜⾜䜟䜜
䝺䝗䜻䝅䞁䝣䜯䝭䝸䞊䝍䞁䝟䜽㉁䛜᳜≀ⴥ⥳యෆ䛷䛹䛾䜘䛖
䜛䚹᳜≀䛻䛸䛳䛶ගྜᡂ䛿㠀ᖖ䛻㔜せ䛺ᶵ⬟䛷䛒䜛䛯䜑䚸
䛻౑䛔ศ䛡䜙䜜䛶䛔䜛䛾䛛䚸䛭䛾ศᏊᶵᵓ䚸⏕⌮Ꮫⓗព
ᵝ䚻䛺ไᚚᶵᵓ䜢ഛ䛘䛶䛔䜛䚹⚾䛯䛱䛿䛣䛾୰䛷䜒㧗➼
⩏䜢᫂䜙䛛䛻䛩䜛䚹㻌
᳜≀ⴥ⥳య䛻䛚䛡䜛䝺䝗䝑䜽䝇ไᚚᶵᵓ䛻䛴䛔䛶䚸䛭䛾
䠎䠅ⴥ⥳య䝏䝷䝁䜲䝗⭷䜢௓䛧䛯㑏ඖຊఏ㐩ᶵᵓ䛾ゎ᫂㻌
⏕⌮ᶵ⬟䛸ศᏊ䝯䜹䝙䝈䝮䛾ゎ᫂䜢┠ᣦ䛧䚸◊✲䜢⾜䛳
ⴥ⥳య䛿䚸እໟ⭷䚸ෆໟ⭷䛸䛔䛖஧ᯛ䛾⭷䛻ᅖ䜎䜜䛯
䛶䛔䜛䚹㻌
䜸䝹䜺䝛䝷䛷䛒䜛䚹ⴥ⥳య䛿䚸䛥䜙䛻䝏䝷䝁䜲䝗⭷䛸࿧䜀
㻌 ⴥ⥳య䛾䝺䝗䝑䜽䝇ไᚚᶵᵓ䛷䛿䚸䝏䜸䝺䝗䜻䝅䞁䛸࿧
䜜䜛⭷䜢ᣢ䛳䛶䛚䜚䚸ᙧែୖ䜒」㞧䛺䜸䝹䜺䝛䝷䛷䛒䜛䚹
䜀䜜䜛䝍䞁䝟䜽㉁䛜䛭䛾ไᚚ䛻୰ᚰⓗ䛺ᙺ๭䜢ᯝ䛯䛩䚹
᫨䛸ኪ䛸䛷኱䛝䛟䝺䝗䝑䜽䝇⎔ቃ䛜ኚ໬䛩䜛ⴥ⥳య䝇䝖䝻
ᮏ◊✲ᐊ䛜Ⓨ㊊ 䛧䛶䛛䜙䚸䝏䜸䝺䝗䜻䝅䞁䝣䜯䝭䝸䞊䝍䞁
䝬⏬ศ䛸䛿ᑐ↷ⓗ䛻䚸䝏䝷䝁䜲䝗⭷䜢㝸䛶䛯䝏䝷䝁䜲䝗䛾
䝟䜽㉁䛾⏕⌮Ꮫ ⓗᶵ⬟䛾ゎ ᯒ䜢୰ᚰ䛸䛧䛶䚸௨ୗ䛾ල
ෆഃ䠄䝏䝷䝁䜲䝗ෆ⭍䠅䛾䝺䝗䝑䜽䝇≧ែኚ໬䛿䜋䛸䜣䛹▱
యⓗ䛺◊✲㡯┠䜢タᐃ䛧䚸◊✲䜢㐍䜑䛶䛔䜛䚹㻌
䜙䜜䛶䛔䛺䛔䚹⚾䛯䛱䛿䚸䝏䝷䝁䜲䝗ෆ⭍䛻䜒䝏䜸䝺䝗䜻䝅
㻌
䞁ᵝ䝍䞁䝟䜽㉁䛜ᒁᅾ䛩䜛䛣䛸䜢ド᫂䛧䚸䛣䜜䛜䝏䝷䝁䜲䝗
ෆ⭍䛷ᶵ⬟䛧䛶䛔䜛䛣䛸䜒᫂䜙䛛䛻䛧䛯䚹㑏ඖຊ䛾⵳✚
䛾䛺䛔䝏䝷䝁䜲䝗ෆ⭍䛷䚸䝏䜸䝺䝗䜻䝅䞁䛾䜘䛖䛺㓟໬㑏
ඖ䝍䞁䝟䜽㉁䛜ᶵ⬟䛩䜛䛯䜑䛻䛿㑏ඖຊ䛾౪⤥䛜ᚲせ
䛷䛒䜛䚹䝏䝷䝁䜲䝗ෆ⭍䛷ᚲせ䛸䛺䜛㑏ඖຊ䜢䝇䝖䝻䝬䛛䜙
ఏ㐩䛩䜛ศᏊ䝯䜹䝙䝈䝮䚸䛚䜘䜃䛭䛾⏕⌮Ꮫⓗ䛺ព⩏䜢
᫂䜙䛛䛻䛩䜛䚹㻌
㻌
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
㻌 䠍䠅ⴥ⥳య䝇䝖䝻䝬䛻䛚䛡䜛䝏䜸䝺䝗䜻䝅䞁䝣䜯䝭䝸䞊䝍䞁
䝟䜽㉁䛾ᶵ⬟ไᚚᶵᵓ䛾ゎ᫂㻌
㧗➼᳜≀䛾䝰䝕䝹᳜≀䛷䛒䜛 㻭㼞㼍㼎㼕㼐㼛㼜㼟㼕㼟㻌㼠㼔㼍㼘㼕㼍㼚㼍 䛷
䛿䚸䠑䜾䝹䞊䝥 㻝㻜 ✀㢮䛻䛚䜘䜆䝏䜸䝺䝗䜻䝅䞁䜰䜲䝋䝣䜷
㻌
䞊䝮䛾Ꮡᅾ䛜᫂䜙䛛䛸䛺䛳䛶䛔䜛䚹䛣䜜䜙ከ䛟䛾䜰䜲䝋䝣䜷
䠍䠅ⴥ⥳య䝇䝖䝻䝬䛻䛚䛡䜛䝏䜸䝺䝗䜻䝅䞁䝣䜯䝭䝸䞊䝍䞁䝟
䞊䝮䛾ᶵ⬟ศᢸ䛜䚸ⴥ⥳యෆ䛷䛾ྛ✀⤒㊰䜈䛾㑏ඖຊ
䜽㉁䛾ᶵ⬟ไᚚᶵᵓ䛾ゎ᫂㻌
౪⤥䛾౑䛔ศ䛡䜢ྍ⬟䛻䛧䛶䛔䜛䛸⪃䛘䛶䚸䛣䜜䜙䛾䝍䞁
ⴥ⥳య䝇䝖䝻䝬䛷䛿䚸ගྜᡂ䛾⾜䜟䜜䜛᫨䛸ኪ䛸䛷኱
䝟䜽㉁䛾ᶵ⬟ゎᯒ䜢㐍䜑䛯䚹 㼙 ᆺ䝏䜸䝺䝗䜻䝅䞁䛻㛵䛧
䛝䛟䝺䝗䝑䜽䝇≧ែ䛜ኚ໬䛩䜛䚹ගྜᡂ䛾⾜䜟䜜䜛᫨䛻䛿䚸
䛶䛿䚸䝅䝻䜲䝚䝘䝈䝘䛷 㼙 㻝㻘㻌㼙 㻌㻞㻘㻌㼙 㻌㻟㻘㻌㼙 㻌㻠 䛾䠐✀㢮䛾䜰䜲
ගྜᡂ㟁Ꮚఏ㐩⤒㊰䛛䜙⏕䛨䜛㟁Ꮚ䛷 㻺㻭㻰㻼㻴 䜢⏘⏕
䝋䝣䜷䞊䝮䛖䛱 㼙 㻝㻘㻌 㼙 㻞㻘㻌 㼙㻠 䛻ኚ␗䜢ᣢ䛴䝅䝻䜲䝚䝘䝈䝘
䛩䜛䛯䜑䚸䝇䝖䝻䝬⏬ศ䛿㑏ඖ ⓗ䛺≧ែ䛻䛒䜛䚹᫨ 䛾㑏
ኚ␗య䜢ྲྀᚓ䛧䚸䛣䜜䜙䛾ゎᯒ䜢㐍䜑䛶䛔䜛䚹䛣䛾
ඖⓗ≧ែ䛾䛸䛝䛻ⴥ⥳య䝇䝖䝻䝬䛻ᒁᅾ䛩䜛䝏䜸䝺䝗䜻
㼠㼞㼤㼙㻝㻞㻠 ኚ␗య䛿ಶయ䛜ᑠ䛥䛟䚸ගྜᡂ㟁Ꮚఏ㐩㏿ᗘ
䝅䞁䛿䚸䜹䝹䝡䞁䝃䜲䜽䝹䛺䛹䛾㓝⣲䜢㑏ඖ䛧άᛶ໬䛩
䜔Ⅳ㓟ᅛᐃ཯ᛂ䛻䜒ᙳ㡪䛜ぢ䜙䜜䛯䚹⌧ᅾ䚸䛣䜜䜙䛾⌧
䜛䚸䝨䝹䜸䜻䝅䝺䝗䜻䝅䞁䜢䛿䛨䜑䛸䛩䜛άᛶ㓟⣲✀ᾘཤ
㇟䛜ほᐹ䛥䜜䜛⌮⏤䜢䚸ศᏊ䝯䜹䝙䝈䝮䛾ほⅬ䛛䜙᫂䜙
⣔㓝⣲䜈཯ᛂ䛻ᚲせ䛺㟁Ꮚ䜢౪⤥䛩䜛䚸䝏䝷䝁䜲䝗ෆ⭍
䛛䛻䛩䜛䛣䛸䜢┠ᣦ䛧䛶◊✲䜢㐍䜑䛶䛔䜛䚹䜎䛯䚸㼀㻙㻰㻺㻭
䜈䛾㑏ඖຊ౪⤥⤒㊰䜈㟁Ꮚ䜢Ώ䛩䚸䛺䛹䛥䜎䛦䜎䛺ሙ㠃
ᤄධኚ␗ᰴ䛾ゎᯒ䛻ຍ䛘䛶䚸㻾㻺㻭㼕 ἲ䛻䜘䜛 䡉 ᆺ䝏䜸䝺
䝗䜻 䝅䞁䛾ኚ ␗ య 䜒ྲྀ ᚓ 䛧䚸 ゎ ᯒ 䜢 ⾜ 䛳 䛯䚹䛣䛱 䜙䛿䚸
reducing equivalents are produced from photosystem and
㼀㻙㻰㻺㻭 ᤄධኚ␗ᰴ䛻ẚ䜉䚸 䡉 ᆺ䝏䜸䝺䝗䜻䝅䞁䛾⵳✚
used to produce the reductant NADPH. NADPH is
䝍䞁䝟䜽㉁㔞䛜䜘䜚ᑡ䛺䛟䚸⾲ ⌧ᆺ䛜䛿䛳䛝䜚䛸⌧䜜䚸ಶ
further used for the reduction of CO2 in the chloroplast
య䜒㠀ᖖ䛻ᑠ䛥䛟䚸ᙅග᮲௳䛷䛺䛟䛶䛿⏕⫱䛜䛷䛝䛺䛔䛣
stroma. A portion of the reducing equivalents is also
䛸䛜䜟䛛䛳䛯䚹㻌
utilized
for
reduction
of
stroma
thioredoxins.
Thioredoxins transfer reducing equivalents for regulation
of thiol-enzymes, scavenging for reactive oxygen species,
or reducing equivalents transfer system across thylakoid
membranes. How stromal thioredoxins recognize various
target proteins in stroma, without being confused?
Arabidopsis thaliana have five groups of stromal
thioredoxins. We have focused m-type thioredoxin, a
member of stromal thioredoxin family proteins. T-DNA
insertion lines of m-type thioredoxin in A. thaliana were
screened. The trxm124 mutant showed the growth defect
and the decreased chlorophyll content, compared with
the wild type. We also made m-type thioredoxins
deficient line by RNAi method. These RNAi lines have
showed severe phenotype in growth.
䠎䠅ⴥ⥳య䝏䝷䝁䜲䝗⭷䜢௓䛧䛯㑏ඖຊఏ㐩ᶵᵓ䛾ゎ᫂㻌
㻌 ⚾䛯䛱䛾䛣䜜䜎䛷䛾◊✲䛛䜙䚸㑏ඖຊ䛾⵳✚䛾䛺䛔䝏
2: Physiological role and molecular mechanism of
䝷䝁䜲䝗ෆ⭍䛻㑏ඖຊ䜢౪⤥䛩䜛䝅䝇䝔䝮䛾Ꮡᅾ䛜♧၀
reducing
䛥䜜䛶䛔䜛䚹⏕໬Ꮫⓗ䛺ゎᯒ䛺䛹䛛䜙䚸䝏䝷䝁䜲䝗⭷䝍䞁
membranes in chloroplasts.
䝟䜽㉁䛷䛒䜛 㻯㼏㼐㻭 䛜䝏䝷䝁䜲䝗⭷䜢㉸䛘䜛㑏ඖຊཷ䛡Ώ
In contrast to redox state control in stroma side,
䛧䛾ೃ⿵ᅉᏊ䛷䛒䜛䛣䛸䛜᫂䜙䛛䛸䛺䛳䛶䛝䛯䚹ᮏᖺᗘ䛿䚸
knowledge pertaining to redox regulation on the lumenal
䝅䝻䜲䝚䝘䝈䝘䛾 㻯㼏㼐㻭 Ḟኻኚ␗య䛻䛚䛡䜛᳜≀య䛾⾲
side of the thylakoid membrane remains very limited. We
⌧ᆺ䛾ほᐹ䜢⾜䛳䛯䚹䛭䛾⤖ᯝ䚸㻯㼏㼐㻭 Ḟኻኚ␗ᰴ䛷䛿䚸
previously demonstrated that a thioredoxin-like protein
ᡂ㛗䛜㐜䛟䚸ⴥ䛻䛿ග㜼ᐖ䛾ᙳ㡪䛜ほᐹ䛥䜜䛯䚹㻌
is located in the thylakoid lumen and can function as a
㻌
reducing equivalent carrier to protein targets located in
㸱㸬Research projects and annual reports
the lumen. In order to function as a carrier of reducing
We have been setting our research theme on the
equivalents in the thylakoid lumen, a thioredoxin-like
functional regulation of higher plant chloroplast.
protein in thylakoid lumen side in turn must receive
equivalent
transfer
system
on
thylakoid
Plants have photosynthetic ability to convert carbon
reducing equivalents. These results suggest that higher
dioxide into organic compounds, especially sugars, as
plant chloroplasts possess a reducing equivalent transfer
unique feature. The photosynthesis in higher plants
system which operates across the thylakoid membrane
occurs
in
chloroplasts
which
are
comprised
of
from the stroma to the lumenal side. We analyze the
multilayered membranes, and pushes forward carbon
physiological role and molecular mechanism of the
dioxide fixation. Chloroplasts have various regulation
reducing
mechanisms of photosynthesis that is an important
membrane.
equivalent
transfer
system
across
the
function for plants. Particularly, we focus on redox
CcdA, which is a candidate for this system, was
regulation in modulation system of higher plant
examined a contribution for reducing equivalent transfer
chloroplast, and have major two research projects as
assay in vitro, using isolated thylakoid membranes. If
follows:
both a lumenal thioredoxin-like protein and CcdA
1: Functional analysis of stromal thioredoxin family
protein function in the same reducing equivalent transfer
proteins in redox regulation system.
pathway, reduction of a disulfide bond in the CcdA
The redox state of higher plant chloroplasts fluctuates
molecule should be promoted by stromal thioredoxin. We
widely under light and dark conditions. In the light,
demonstrated CcdA could be reduced, in which a
ㄢ㢟ྡ䠖ⴥ⥳య䝇䝖䝻䝬䛛䜙䝏䝷䝁䜲䝗ෆ⭍䜈䛾㑏ඖຊఏ㐩ᶵ
lumenal thioredoxin-like protein was reduced. In this
ᵓ䛾ゎ᫂㻌
year, we screened the ccdA deficient T-DNA insertion
◊✲௦⾲⪅䠖ᱩᕝ཭Ꮨ㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻞㻙㻞㻠 ᖺᗘ㻌 㻔㻟 ᖺ㻕㻌
㻌
lines in Arabidopsis thaliana and observed the ccda
mutant phenotype.
䠎䠅㻌 䛭䛾௚㻌 ◊✲ᐊ䝯䞁䝞䞊䛾෗┿㻌
㻌
䠐䠊ㄽᩥ䠈ⴭ᭩䛺䛹㻌
K. Yoshida, K. Noguchi, K. Motohashi, T. Hisabori: Systematic
Exploration of Thioredoxin Target Proteins in Plant
Mitochondria. Plant Cell Physiol. 54, 875-892 (2013)
Y. Taira, Y. Okegawa, K. Sugimoto, M. Abe, H. Miyoshi, T.
Shikanai: Antimycin A-like molecules inhibit cyclic electron
transport around photosystem I in ruptured chloroplasts. FEBS
Open Bio 3, 406-410 (2013)
K. Sugimoto, Y. Okegawa, A. Tohri, T. A. Long, S. F. Covert, T.
Hisabori, T. Shikanai: A single amino acid alteration in PGR5
confers resistance to Antimycin A in cyclic electron transport
around PSI. Plant Cell Physiol. 54, 1525-1534 (2013)
㻌
㻌
㻌
䠑䠊Ꮫ఍Ⓨ⾲䛺䛹㻌
㻌
ᱩᕝ཭Ꮨ䚸ᮏᶫ೺: 䝅䝻䜲䝚䝘䝈䝘䛾䝺䝗䝑䜽䝇ไᚚ䛻䛚䛡䜛䡉 ᆺ
㻌
Trx䛾ᙺ๭ ➨55ᅇ᪥ᮏ᳜≀⏕⌮Ꮫ఍ᖺ఍䠈ᐩᒣᕷ䠈2014.
㻌
3.18-20
ᱩᕝ཭Ꮨ䚸ᮏᶫ೺: 䝅䝻䜲䝚䝘䝈䝘䛻䛚䛡䜛ⴥ⥳య䝏䜸䝺䝗䜻䝅
䞁䛾⏕⌮Ꮫⓗゎᯒ ➨85ᅇ᪥ᮏ⏕໬Ꮫ఍䠈ᶓ὾ᕷ䠈2013.
9.11-13
ᱩᕝ཭Ꮨ䚸ᮏᶫ೺:㻌 䝅䝻䜲䝚䝘䝈䝘䛾mᆺ䝏䜸䝺䝗䜻䝅䞁ኚ␗ᰴ
䛾ゎᯒ ➨䠐ᅇ᪥ᮏගྜᡂᏛ఍ᖺ఍䠈ྡྂᒇᕷ䠈2013. 5.31- 6.
1
ᱩᕝ཭Ꮨ䚸ᮏᶫ೺: ⴥ⥳య䝇䝖䝻䝬䛻䛚䛡䜛m-type 䝏䜸䝺䝗䜻䝅
䞁䛾⏕⌮ᶵ⬟䛾ゎᯒ➨54ᅇ᪥ᮏ᳜≀⏕⌮Ꮫ఍ᖺ఍䠈ᒸᒣᕷ䠈
2013. 3.21-23
㻌
䠒䠊䛭䛾௚≉グ஦㡯㻌
䠍䠅㻌 እ㒊㈨㔠
⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ᣮᡓⓗⴌⱆ◊✲㻌
ㄢ㢟ྡ䠖ගྜᡂ⏘≀ྍど໬䛾䛯䜑䛾⺯ග䝥䝻䞊䝤㛤Ⓨ㻌
◊✲௦⾲⪅䠖ᮏᶫ೺㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞䠑㻙㻞㻢 ᖺᗘ㻌 㻔㻞 ᖺ㻕㻌
Ꮫ⾡◊✲᣺⯆㈨㔠䠄᪥ᮏ⚾❧Ꮫᰯ᣺⯆䞉ඹ῭஦ᴗᅋ䠅㻌
ㄢ㢟ྡ䠖᳜≀䛾ගྜᡂ䜢ไᚚ䛩䜛䝯䜹䝙䝈䝮䛾ゎ᫂㻌
◊✲௦⾲⪅䠖ᮏᶫ೺㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞䠑ᖺᗘ㻌 㻔䠍ᖺ㻕㻌
⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ᇶ┙◊✲䠄㻯䠅㻌
ㄢ㢟ྡ䠖㧗➼᳜≀ⴥ⥳య䛻䛚䛡䜛䝏䜸䝺䝗䜻䝅䞁䝣䜯䝭䝸䞊䝍
䞁䝟䜽㉁䛾ᶵ⬟ศᢸゎᯒ㻌
◊✲௦⾲⪅䠖ᮏᶫ೺㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻞㻙㻞㻠 ᖺᗘ㻌 㻔㻟 ᖺ㻕㻌 㻌
⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ⱝᡭ◊✲䠄㻮䠅㻌
Prof. Hiroshi Yamagishi, Agr. Dĸ
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ŷœūŝũŒźōĸ
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ŝŤī t Í t
ŗ‰ŸŖŮŭŹŌŖŧ•ìůIJHŗÝŹĕųŻŧ
ůØçĭΞ¸ŒũŌyŝ
ĭÒƹƲłŃ ľ ƳųŪž
ŧőźōĸ
³nŝŤōØçĭÎūŢůmůƤƗƌƯƘƫſůĞ
ĸ
TŮŧŒũƍƎƯþ’žóŦŤūśżŌŀ ĞTŗü
ĸ
Î ůƞƯƘžőŽš€ ŧƟƓƱƯžË ŝŌƺĞ T ŗ
Research projects and annual reports
ØçĭβŽůƞƯƘƟƓƱƯžËŝũŒŤōŜŸŮśů
In the field of plant breeding, F 1 hybrids have many
ŷœŭƤƗƌƯƘƫſĞTůŸĘŰyŝ
ĭžÛũŶŌX
genetic advantages and contribute to the increase of
YŝũmŮěŜŻũŒźśūŗ‰ŸŖŮŭŦŤōŢů
worldwide crop production.
‡ŪŌłŃ Ľ ŮŧŒũíÔÍtžý]ŝŤūśżŌ
F 1 hybrid production, cytoplasmic male sterility (CMS)
XYŝũīt͞˺ūŌğ!¿ŮÍtž>o
is the most useful genetic characteristic.
şźūŗăŵŸŻŤōśůŷœŭŌğ!3Í+ů/?
practical importance of the CMS, it is useful to study the
žĆ–şźūūŶŮŌŜŸŮyŝ
ĭžĚŵũŌZ¸¿ŭ
interactions between nuclear genes and mitochondrial
ītÍÕÞžħ¾ŝŷœūŝũŒźōĸ
ones
ĸ ųŤŌÿůØçĭÎūŢůmŮ²ŽůƤƗƌƯƘ
molecular and evolutional genetics.
ƫſƋƜƥůŸĘžŌůſƠƪƙ̛±ůƤƗƌƯƘƫſ
been studying the CMS of various plants both in order to
ū¨đşźŤŵŮŌQřůſƠƪƙ̛±ŪƤƗƌƯƘƫſ
know the evolutional processes and to exploit new
ƋƜƥůMJġ"žªYŝŤōşŭŽťŌØçĭÎ
breeding materials.
ů ‡ ůü ŪőźƇƨƢƖŮ' ŔũŌƝƉƍƀŌƉƮƆƪ
sterile materials, we are utilizing organelle genome
ƏŮŧŒũƤƗƌƯƘƫſůƋƜƥþ’žóŦŤōĸ
engineering methods such as cell fusion, and cytoplasm
ƷƳØ ç č á ƒ ŮŷźƔƀƌƯŕŷŲƙƑůī t Í ů
substitution.
ħ¾ĸ
ĸ ƙƑůØ ç č ī t Í ůœťŌí Ô l w G ůī
from
scientific
For the efficient and stable
view
points,
Besides the
especially
for
Thus, we have
For the establishments of new male
1) Ogura CMS and its fertility restoring genes.
Ogura CMS found in a Japanese radish is the most
tÍŮ_şźÍt>oĞTů ńŇŁ ƣƱƅƱžħ
important
¾ ŝŤōşŪŮn ŸŻũŒźƣƱƅƱŰŌ ´ ŭŗŸÚ
worldwide.
ƒ Ŕ ž¶ ŞźŶůŪőŦŤōŢśŪŌśŻŸůƣƱƅ
and differentiations of Ogura CMS gene, orf138.
ƱŷŹŜŸŮÍt>oĞTūkřęĥŝŤ ńŇŁ ƣƱƅ
Whereas, we found that various wild and cultivated
Ʊžœ×ŝŤūśżŌƖ ĻĿľ ŮŕŒũřڃ
radishes possess fertility restoring genes for Ogura CMS.
Ŕŗý]ŜŻŭŒ ńŇŁ ƣƱƅƱŗ¾ùŜŻŤōŢś
Hitherto, two fertility restoring genes were known.
ŪśůƣƱƅƱů ňʼnň +žĚŵŤōĸ
One is orf687 in a Chinese variety, and another is Rft
one
in
Cruciferous
plants,
being
used
We have been studying the distributions
distributed in Japanese wild radishes.
We observed that
a European radish cultivar, ‘Kurodaikon’, has a fertility
H. Yamagishi, S. R. Bhat: Cytoplasmic male sterility in
restoring gene different from both of orf687 and Rft.
Brassicaceae crops. Breeding Science. 64(No.1), in press ”
We, thus, determined the DNA sequence of this new
‡•
gene.
From the results we estimated the genetic
ĸ
processes in which the fertility restoring gene of
3/,+ĸ
‘Kurodaikon’ was produced.
ĔÆõŌšÂ¤Ōac.Ō^Epƻ—ƋƜƥŸwŮŷŹĜŒž
ËşEmmer-DinkelƌƥƈůƤƗƌƯƘƫſůQGōˆåÎV
2) New male sterile plants derived from the cell fusion.
Ò124>ć®ƴķdÅƴ2014.10.12-13
We obtained somatic hybrids showing male sterility
between Arabidopsis thaliana and cabbage varieties
(Brassica oleracea).
bğÆiŌ¹âóŌac.Ō^Epƻ¦ƏƱƉƃƯƍƱž
¸ŒŤƔƀƌƯůƤƗƌƯƘƫſƋƜƥůġ"þ’ƷƻįĦƔƀƌƯ
It was found by the molecular
ůƤƗƌƯƘƫſƋƜƥġ"ůªYōˆåÎVÒ124>ć
analyses of their mitochondrial genomes that the male
®ƴķdÅƴ2014.10.12-13
sterile hybrids contain the various novel genome
structures of mitochondria.
Progenies of the somatic
NO :™
0„=x^ƒš`c1€x
hybrids were obtained by successive back-crosses with B.
tZ5{fn$!#),š-‚‰Ak1
oleracea.
dNqg9Juy[ |——@6‘ˆm2–hlP–
So far, the pollen fertility was investigated in
the BC 4 progenies.
”]Tˆm•
The BC 4 progenies were segregated
into completely male sterile plants and partially fertile
plants.
However, all the BC 4 progeny plants had the
identical structure of mitochondrial genome.
Further
4/*-
ƵƳĸ PğċĤ
back-crosses and observation of pollen fertility are now
Ē“©·ÄưƋƜƥuKž«¸ŝŤĒ¼·±ů¦¶·J
undertaken.
À|ôůħ¾ơƮƐƂƉƗƲCî±ůŽ¸ĞTů7Yūƽ
3)
CMS
of
radish
and
eggplant
by
cytoplasm
ƾƼƣƱƅƱůħ¾Ƴĸ
ąĴ8ƻƙƑŮ়íÔÍt>oĞTů-Įĸ
substitutions.
ÈÐöäƻac.ƴ1nfgƻņļľƲĻ fƳĸĸ
With the purpose to enlarge the numbers of CMS
material
plants,
we
are
analyzing
the
ĸ
molecular
characteristics of alloplasmic radishes and eggplants
ƶƳĸ Çĉ£Óĸ ŭŝĸ
under the collaborative projects with other institutions.
ƷƳĸ VP«)ĸ ƻ‹ejqsH†&)"uy
i4E
We found unique orfs in male sterile alloplasmic lines
8MXVoC“_pq}vz\…‘
both in radishes and eggplants.
rŒ?H>
By the studies of their
expressions, it was suggested that they are promising
`c€xJ2R/
candidates of causal genes of CMS.
ƸƳĸ 2ČÓĸ ŭŝĸ
Furthermore, we
exploited DNA markers of fertility restorer genes of
eggplants.
ƹƳĸ Ţůĸ ĸ
7J” Q b•
The markers would be useful to identify the
restorer genes and to clarify the mechanisms of CMS and
ĸ
fertility restoration.
ĸ
ĸ
ĸ
2/
.,+
M. Yoshimi, Y. Kitamura, S. Isshiki, T. Saito, K. Yasumoto, T.
Terachi, H Yamagishi: Variations in the structure and
transcription of the mitochondrial atp and cox genes in wild
Solanum species that induce male sterility in eggplant (S.
melongena). Theoretical and Applied Genetics. 126, 1851-1859
KcaG+LB W+NO :™*(C’Y.
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ື≀⏕࿨་⛉Ꮫ⛉
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ࡢゎ᫂ࡢࡓࡵࡢࣔࢹࣝື≀ࡢ㛤Ⓨࠊឤᰁ⑕ࡢゎ᫂ࠊᐇ㦂་Ꮫࡢᛂ⏝࡟ࡼࡿ㣗ရ࣭
〇⸆࡞࡝ࡢᏳ඲ᛶ☜ಖ࡟ᙺ❧ࡘ◊✲ࢆ⾜ࡗ࡚࠸ࡲࡍࠋ◊✲ෆᐜࡣࠊᅗ࡟♧ࡍࡼ
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⟶㐠ືࡢศᏊᶵᵓࡢゎ᫂ࠊ໬Ꮫ≀㉁ࡢ㣗ရ࡬ࡢᏳ඲ᛶࠊ⑓ែࣔࢹࣝື≀ࡢ㛤Ⓨ
࡞࡝࡟ࡘ࠸࡚ࠊศᏊࣞ࣋ࣝ࠿ࡽಶయࣞ࣋ࣝࡲ࡛◊✲ࢆ㐍ࡵ࡚࠸ࡲࡍࠋࡑࡋ࡚ࠊ
ே㢮ࡢ⏕࿨࡜೺ᗣ࡟ᙺ❧ࡘ⏕࿨་Ꮫ࡬ࡢᛂ⏝ࢆ┠ᣦࡋ࡚ࠊୡ⏺ࣞ࣋ࣝࡢᅜෆ᭷
ᩘࡢᐇ㦂᪋タࡢࡶ࡜࡛◊✲ࢆᒎ㛤ࡋ࡚࠸ࡲࡍࠋࡲࡓࠊி㒔ᗓࠊி㒔ᕷࠊ኱㜰ᗓ
❧኱Ꮫ࡜ࡢᏛ⾡஺ὶ༠ᐃࢆ⤖ࡧࠊ≉࡟ឤᰁ⑕࡟㛵ࡍࡿ◊✲ࢆ✚ᴟⓗ࡟㐍ࡵࠊࢢ
࣮ࣟ࢝ࣝ࠿ࡽࢢ࣮ࣟࣂࣝࡲ࡛ࡢ◊✲ࢆᒎ㛤ࡋ࡚࠸ࡲࡍࠋ
࠙ᩍ⫱ࠚ
ୗ⾲ࡣࠊື≀⏕࿨་⛉Ꮫ⛉ࡢᩍဨࡀᢸᙜࡍࡿᤵᴗ⛉┠࡛ࡍࠋᮏᏛ⛉ࡣࠊᐃဨ 35
ྡ࡟ᑐࡋ࡚ 12 ྡࡢᩍဨࡀㅮ⩏ࠊᐇ⩦ࢆᢸᙜࡋࠊධᏛ࠿ࡽ༞ᴗࡲ࡛ᚭᗏࡋ࡚ᑡᩘ
⢭㗦ᩍ⫱ࢆᐇ᪋ࡋ࡚࠸ࡲࡍࠋ≉࡟ࠊᏛ⛉ࡢ≉ᛶୖࠊᐇ⩦࡟㔜ࡁࢆ࠾ࡁࠊ1 ᖺ⏕࠿
ࡽᐇ⩦ࢆጞࡵࠊᏛᖺࡀ㐍ࡴ࡟ࡘࢀ࡚ࡼࡾᑓ㛛ⓗ࡛㧗ᗘ࡞ᐇ⩦ࢆ⾜࠸ࡲࡍࠋ3ࠊ4
ᖺ⏕ࡢᇶ♏ࠊᛂ⏝≉ู◊✲࡛ࡣࠊᩍဨ 1 ྡ࡟ 3㹼4 ྡࡢᏛ⏕ࢆᑐ㇟࡜ࡋ࡚⣽ࡸ࠿
࡛⾜ࡁᒆ࠸ࡓᣦᑟࢆࡋ࡚࠸ࡲࡍࠋࡲࡓࠊ≉➹ࡍ࡭ࡁᩍ⫱࡜ࡋ࡚ࠊ㫽ྲྀ኱Ꮫࠊᒱ
㜧኱Ꮫ࡜㐃ᦠᩍ⫱ࢆ⾜ࡗ࡚࠸ࡲࡍࠋ࣒࢝ࣜ࢟ࣗࣛᵓᡂࡣࠊึᖺᗘࡣ⏕≀Ꮫࠊ໬
Ꮫ㏻ㄽࠊ⏕໬Ꮫᐇ⩦࡞࡝ࡢᇶ♏ࢆᏛࢇࡔࡢࡕࠊ2 ᖺ⏕࠿ࡽゎ๗Ꮫࠊ⏕⌮Ꮫࠊᚤ⏕
≀Ꮫࠊື≀⦾ṪᏛᐇ⩦࡞࡝ࡢᇶ♏ᑓ㛛⛉┠ࢆᏛࡧࡲࡍࠋࡑࡢᚋࠊࡼࡾᑓ㛛ᛶࡢ
㧗࠸ࠊ⾨⏕Ꮫࠊឤᰁ⑕ᏛࢆᏛࡧࠊ3 ᖺ⏕ࡢ⛅Ꮫᮇ࠿ࡽྛ◊✲ᐊ࡟ศᒓࡋࠊᇶ♏≉
ู◊✲ࢆᏛ⩦ࡋࠊ4 ᖺ⏕࠿ࡽࡼࡾᑓ㛛ᛶࡢ㧗࠸ᛂ⏝≉ู◊✲࡟ྲྀࡾ⤌ࡳࡲࡍࠋࡲ
ࡓࠊ3 ᖺ⏕ࡢ⛅Ꮫᮇ࡟ࡣᐇ㦂ື≀୍⣭ᢏ⾡⪅㈨᱁ヨ㦂ࢆཷ㦂ࡍࡿࡇ࡜ࡀฟ᮶ࠊᖹ
ᡂ 25 ᖺᗘࡣ 17 ྡࡶࡢྜ᱁⪅ࢆฟࡋ࡚࠸ࡲࡍࠋ኱Ꮫ㝔࡬ࡢ㐍Ꮫ⪅ࡶከࡃࠊ♫఍
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#+"&( Professor Koichi Otsuki, DVM, Ph D
ĦħĨİıħIJİıijĜİĪĜĤįĬĮħĭĜĥijīĬĩįĩ
1:&(-
this virus. Our research base is the overseas research station
1970 §](‰o#ŃÏ*q‹$á)ņ$ņ.PDM1
“Friendship Laboratory” opened by Nagasaki University in the
P7/.M:éÝ"(%#sŁņ.PDM1P7/.M:$
National Institute of Hygiene and Epidemiology in Ha Noi.
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K. Hotta, H. Takakuwa, T. Yabuta, T. T. Ung, T. Usui, H. L. Nguyen,
T. T. Le, M. Q. Le, T. Yamaguchi, K. Otsuki, T. Ito, T. Murase, T.
2. &(
äx‚ʼnĻľŒĚŗƀŴžŚƀšñˆŔĵ­®£…Mņßň
ŃŅĺŒĶ¢őĚĽĕ„ŁŒ ĞĞ ~ļŐ&WßŔDŁŒ ġ ~ō
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ŐÑÒŀŅEwŀŅĺŒĶĚ+=BøBĀĊJĚ³„¬û
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Āŋ-ØňŏŊļŐIąîʼnГâŀŅĺŒĶĜ
Ĝ Ĝ jŗƀŴžŚƀšŘŗžŤÐƒŊĆºŋĵę‹smĵݲ
ÁÇ3ŐŇ/ÁÇŔEwŀŅĺŒĶļŐoĿœŒķ
ňÆĔŊЃŊjŘŗžŤ±ʼnńĺŅŒëŔEwŀŅĺŒĶ
ÁÇg†ŊĀŋĵŇ/ņ©í ēŏßňŃŅĺŒĶĜ
Yamashiro. Antibody survey on avian influenza viruses using egg
yolks of ducks in Hanoi between 2010 and 2012. Veterinary
Microbiology. 2013. 166, 179-183ƃòuƄ
H. Takakuwa, T. Yamashiro, M. Q. Le, L. S. Phuong, H. Ozaki, R.
Tsunekuni, T. Usui, H. Ito,T. Yamaguchi, T. Ito, T. Murase, E. Ono,
K . Otsuki. The characterization of low pathogenic avian influenza
viruses isolated from wild birds in northern Vietnam from 2006 to
2009. ƃComparative Immunology, Microbiology and Infectious
Diseases. 2013. 36, 581-590ƆƃòuƄ
Y. Fujimoto, K. Ozaki, M. Maeda, K. Nishijima, H. Takakuwa, K.
Otsuki, H. Kida, E. Ono. Resistance to influenza A virus infection
in transformed cell lines expressing an anti-PB2 monoclonal
antibody. Veterinary Journal. 2013. 198, 487-493ƆƃòuƄ
=Ɔ5ņųūʼnº¯ŀŅĺŒ¸)eĚŗƀŴžŚƀš
Ĝ ěŊÁÇ, 88, 14-17, 2013.ƃéïƄ
=:Research projects and annual reports
=Ɔ5ņº¯ŀł¸)eĚŗƀŴžŚƀšƆ
Our research is focussed mainly epizootiology on avian
Ĝ ėěŊ*, No. 616, 46-49, 2013.ƃéïƄ
influenza (AI). We are analysing some properties of AI viruses
=ƆĚŗƀŴžŚƀšŊċŊ-ØeĜ ųūļŐųūŌŊ
isolated from a few kinds of migratory waterfowls flying from
Ĝ ŲƀŪŸŨşŋöŒŊļƋžõŇ¯›,Ĝ No. 312,Ĝ 2013Ɔ
Siberia or northern China and staying in the Kansai region,
Ĝ ƃéïƄ
particularly Lake Biwa during winter to clarify these isolates from
=Ɔ¬ûf‡¹Ŋ4ő
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an ecological point of view.
Ĝ ťŞŻŽũŖŮŻƂŤſŦƂƆűŗśťŞŻŽũŖ!ĂŊ5čý
We are also collaborating with few companies to develop
Ĝ p("ʼnĈŁŒÁÇñˆ91|ƃZg 24 []uĀÄB¾Á
anti-viral activity-having useful products, that is, we evaluate
Ĝ ÇAìƄƅĄO=B§V'BÁÇh,Ĝ 41-43, 2013ƆƃÓïƄ
materials those were experimentally produced by them, analyse
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mechanisms of this activity and search their applications.
Ĝ º¯ŀł¸)eĚŗƀŴžŚƀšƃH7N9ƄƆā°=B
We are also collaborating with the Avian Zoonoses Research
Ĝ ÉÄBiàÁÇhh9, No. 12, -, 2013.ƃÓïƄ
Centre, Faculty of Agriculture, Tottori University to investigate AI
=ƆĚŗƀŴžŚƀšĸŊ•ŀĺÀóŇŽŤşƁŷůţźƀ
incidence in Viet Nam. We are collecting many foeces and throat
Ĝ ūƆs×Á, No. 492, 83-86, 2013ƆƃéïƄ
swabs from few species of domestic fowls reared in that country to
=Ɔ5ņº¯ŀŅĺŒĚŗƀŴžŚƀšƃH7N9Ƅņ}
isolate AI viruses, and serum samples from them to calculate
Ĝ ùzŐļʼnňŃłĵĈcĽkłœŒÀæƃƄ.Ĝ ěŊÁÇƅ88,
antibody titre to these viruses. We expect to get some useful datum
Ĝ 14-18, 2013.ƃéïƄ
about not only contaminating situation of AI virus in Vietnamese
=Ɔ5ņº¯ŀŅĺŒĚŗƀŴžŚƀšƃH7N9Ƅņ}
poultry industry but also threatening level of human infection with
Ĝ ùzŐļʼnňŃłĵĈcĽkłœŒÀæƃƄ.Ĝ ěŊÁÇƅ88,
Ĝ 14-18, 2013.ƃéïƄ
[ĴªįÑÚðij¨ŒĽøœĉ<P=R#d*Ĺš>RJ
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H. Takakuwa, K. Hotta, T. Yamashiro, M. Q. Le, L. S. Phuong, T. Usui, H.
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Ozaki, H. Ito, T. Murase, T. Yamaguchi, T. Ito, E. Ono, K. Otsuki:
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Distribution of antibodies to Influenza Virus in Wild Birds in Northern
¯n m­þ”ĭ¥ § 4 Ê 26 È
Vietnam in 2011. Asia-Africa Research Forum on Emerging and
’×kSŏņ.PDM1P7#ŊāˆÞ\ÇäþH:
Reemerging Infections 2013, Tokyo, 2013.1.23-24ƆƃŢƀŶţŘŹƄ
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Research projects and annual reports
We investigate the mechanisms of developing
emotional
memory
in
the
hippocampus-amygdala
connections and the acquisition of neural plasticity in the
limbic system.
Furthermore, we aim to develop
diagnostic methods and therapeutic drugs for the relief of
epilepsy, anxiety, and mood disorders based on the
clarification of the mechanism.
JĚƿI*[ĉDŽˆ…‹0»ƥ:[6FEǝ¦ǒ
ƎD`/`0ŜŚ:[FŧË7\>&őÑǝĪƽá
Epileptic model mice and stress-sensitive model
ĵʂckJŦůŽĬIB+DǝƦĜĎŭ“E*[&
mice showing the anxiety, sleep disorder, and hormonal
homeostatic change were used.
iaˆǁ¤Ǘ0±þ:[ć¸ŷŨżÎƯJĀųĴ
check the symptoms of the models by behavioral and
ıJƙĢ
physiological analyses and to clarify causal molecules by
Our approach was to
histological and biochemical analyses.
research and the content were as follows.
The topics of
3: Effect of food intake on stress-sensitive model mice.
1: Clarification of mechanism of epilepsy progression.
Amygdala-kindling model mice are analogous to
The stress-sensitive model mice showed growth
secondarily generalized complex partial seizures and a
inhibition according with decreases of growth hormone
model of temporal lobe epilepsy in humans, showing
and IGF1 within the plasma.
abnormal neural plasticity.
that a specific dietary oil affected depression, anxiety,
Using kindled mice, we have
In this year, we evaluated
found two molecules responsible for epileptogenesis, a
environmental adjustment disorder, and activity.
growth hormone and a sialyltransferase.
we applied for a patent in August, 2013.
First, we found
Then,
We aim to
there is a growth hormone signal system in the brain, and
investigate brain lipid metabolic mechanisms that were
this signal system is deeply related to the development of
generated from food and correlation of the metabolism
neuropsychiatric disorders other than epilepsy.
with emotional behaviors.
We aim
to clarify the whole mechanism of growth hormone
signaling in the brain.
Now we prepare a revised paper.
Second, a sialyltransferase ST3Gal IV deletion failed to
4: Clarification of inhibitory mechanism of epileptic
seizures with botulinum neurotoxin.
develop temporal lobe epilepsy using the ST3Gal IV
gene-deficient mice.
It indicates that ST3Gal IV is an
effective target for treating epilepsy.
Presently, we aim
We
investigated
the
delivery
of
botulinum
neurotoxins directly into the seizure focus of the brain to
prevent epileptic seizures using a model of temporal lobe
to investigate involvement of the sialyltransferase with
epilepsy.
expression of growth hormone in the brain showing
into the hippocampus make seizures disappear in 50% of
epilepsy progression.
mice with kindled seizures.
2: Clarification of the neural network function based on
As a result, administration of the neurotoxin
We aim to investigate the
mechanisms about how the neurotoxin abolishes the
abnormal neural plasticity of epilepsy.
emotions that sialylation controls.
In this year, we
published several data in Toxicon.
Epilepsy patients are at a greater risk for developing
anxiety, depression, psychosis, and learning disorders.
On the other hand, the sialyltransferase gene-deficient
mice showed emotional symptoms including an anxiety
disorder, an environmental adjustment disorder, sleep
disturbance, and hormonal homeostatic disorder.
aim
to
find
the
acceptor
substrate
of
We
alpha
2,3-sialyltransferase and to investigate the effects of
sialylation on the development of epileptogenesis and
emotional symptoms.
We identified that growth
hormone and Igf1 mRNAs were down-regulated in the
brain of the deficient mice, in contrast with tremendous
up-regulation of growth hormone following epileptic
seizures.
These data was summarized and submitted to a
Journal.
On the other hand, the deficient mice showed
decrease of plasma growth hormone and Igf1 according to
growth delay.
Furthermore, failures of post-partum
estrous cycle depending on decrease of FSH, and of
parturition by sustaining plasma progesterone levels on
gestation 19 day were observed.
It proposed that ST3Gal
IV regulates hormonal metastasis on growth hormon-Igf1
axis and progesterone-GnRH system.
preparing a manuscript. Now we are
Kato K, Akaike N, Kohda T, Torii Y, Goto Y, Harakawa T,
Ginnaga A, Kaji R, Kozaki S. Botulinum neurotoxin A2 reduces
incidence of seizures in mouse models of temporal lobe epilepsy.
Toxicon 74:109-15 (2013 11 )9 m2014 1 31 166 6
fckjlgn
ro)\ba(09
_][
so1Zdkheci&9
1. Srimontri P, Nakayama Y, Kurosaka A, Endo S, Sakamoto T,
Itohara S, Hirabayashi Y, and Kato K. Sialyltransferase
ST3Gal IV is involved in temporal lobe epilepsy and its
associated disorders. International Symposium on
Glyco-Neuroscience in Awaji Yumebutai International
Conference Center 2014õ1ħ 9-11ġ (i‹jcƒkn
)
2. ¶ƑÌá ŨżÃ×ăJ‘ĂƪFŨżŵŨŘĆFJdžƶ
ă ķ÷òßáÜã S?8Jœ(ßăŦůƃŦůѸĚė
•İǛĜƾũãšǜ
ǜ )
õ ħ ġǛĐûƨʼnǜ
9
to!,9
1. ¶ƑÌáǝƗñÜƫ ć¸Ɠ¸OJĽƉęǕ·ĬIB+
D ű156ÎġĪŏºãœãƔNjœ 2013õ9ħ21ġ ð
LjÜãǛÂǒǜ
uo^`
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ªÅŦů(( ÇĨ‡‹ƉƬJĴƈƟ¢)ǛŦů™ƕƃǡ
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kt‰kăć¸ŷNJé_ěÍ:[ºƐŖĽƉŻĉŌ ōǔ õ ħ ġ
>;
9
ġĪŶƬãœƟƪÊ
ġĪŨż¹ãœƟƪÊ
džƗçǙ¸ŌŦůœƟƪÊ
Œ¹ãŦůċ ƊũãƀÄŦům‹n èÊŦůÊ
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ĥŴǡKato. K. Underlying Mechanisms of Epilepsy, Edited by:
Fatima Shad Kaneez ISBN 978-953-307-765-9, Publisher: InTech
Ǜ2011 õ 9 ħŜ° 2014 õ 3 ħ 11 ġ 1512 ƾoc‹Šu&ǜ
ƒ~j
http://www.cc.kyoto-su.ac.jp/~kato/Home_J.html/Welcome.html
"#,-".,-/,' "#,-".,-/+(*")!&%($(+&
Assist. Prof. Kenjiro Konno,
○D. V. M., Ph. D., DJCLAMŁ
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ƟI;žŭ¾NƐƃƏƴǏưƟǖŐ ƫǍƾLJǏưƪLjƿƢƲ
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Research projects and annual reports
３．Research projects and annual reports
Laboratory animal medicine is the new
specialty field within laboratory animal science, and
Ł
Ł ƔƄŭƃƏÇ|džƴlją•ƍŭŀħá¿ŸVSĩĆ
also is one of veterinary medicine that is concerned
ƉŲƛŭdžƴljąƊ@•ƍŭǃƤƮƘLjƲƵƏŀħá¿Ə
with the diagnosis, treatment, and prevention of
GƗÓÜaēƊžƈŹƔžƄŮƽƵƘd0ºƏümƉƐŭ
diseases in animals used in research, testing, and
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teaching. And it includes methods to minimize and
prevent pain, discomfort, and distress in research
animals and ways to identify factors that may affect
animal research. The results of these researches
contribute to both the improvement in reliability of
laboratory experiments, and animal welfare.
Assist. Prof. Konno is a diplomate of the
Japanese College of Laboratory Animal Medicine
(JCLAM) and a member of the Japanese Association
of Laboratory Animal Medicine (JALAM). He has
been engaging in the researches of translational
research including regenerative medicine, organ
transplantation, investigation of diseases using
endoscope system “TESALA AE-C1” and
laboratory animals.
inhalational anesthesia using a ventilator.
A main theme of the research in this
Endotracheal intubation was successfully performed
laboratory is a translational research. Translational
on all 10 C57BL/6 mice injected with M/M/B:
research is one of the scientific researches, and its
0.3/4/5 comprised of medetomidine, midazoram and
purpose is practical applications to make findings
butorphanol, at a dose of 0.3 mg/kg + 4.0 mg/kg +
from basic science applicable for human, that is, for
5.0 mg/kg body weight/mouse, respectively. After
our society.
the intubated mice were connected with the
(1) Relationships between blood vessel injury and
inhalational anesthesia circuit and the ventilator,
hyaluronic acid - mouse model of vascular injury -
vital signs were measured until 15 min after the
Although it is thought that hyaluronan
connection. The data with M/M/B: 0.3/4/5 showed
synthase is a very important for the repair of the
stable and normal values, which indicated that this
inner surface of the artery, it has not yet been proved
new endotracheal intubation method was simple,
in detail. Therefore, in order to prove the hypothesis,
reliable and safe, which means that this anesthesia is
with the mouse model of the vascular injury, we are
favorable in regard to the animal’s welfare.
promoting the analysis. Because only arterial
(3) 3D anatomical figures using computer graphical
endothelial cells of the model mouse are curetted
technology
surgically, the making of the rodent model is needed
Interactive visualization is a branch of
for the advanced techniques, knowledges and
graphics in computer science that involves the
experiences. But we have completed the production
creation of graphic illustrations using computers.
of the disease model, and now the process of the
And many animals are used for the purpose of
repair are being analyzing.
education or research, and especially miniature pigs
(2) Anesthesia
are used for translational research. Therefore, by
- endotracheal intubation and
inhalation anesthesia for mice and rats Appropriate and effective anesthesia is critical,
the fusion laboratory animal science and computer
science, we have been preparing 3D anatomical
because it has a strong influence on laboratory
figures of miniature pigs. These results give both
animals, and its affect greatly impacts the
useful information for education and research, and
experimental data. Inhalational anesthesia by
benefits also useful for animal welfare.
endotracheal intubation is currently prevailing in
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general anesthesia and is prefered over injection
85421
A. Hirao, T. Kawarasaki, K. Konno, S. Enya, M. Shibata,
anesthesia, especially for large laboratory animals,
A. Kangawa and E. Kobayashi. Green fluorescent protein
because it is a safe and easy control agent. However,
(GFP) expression patterns in the olfactory epithelium of
it is not common for small laboratory animals,
GFP transgenic cloned Jinhua pigs. Acta Zoologica. 94,
because of the high degree of technical skills
1-11
required.
We assessed the capability of use for
Y. Hirono, Y. Tanahashi, K. Sasaki, K. Konno, Y. Shirai,
mice of the endotracheal intubation by using the
K. Kobayashi, A. Someya, S. Inaga, M. Sakura, E. K.
Pinkerton and M. Takeuchi. Alveolar macrophage
日本実験動物協同組合関西支部会での学術講演
functions and DNA damage in cigarette smoke-exposed
2013年11月29日(金)にキャンパスプラザ京都で開催され
mice. 4, 1-7
た日本実験動物協同組合関西支部会の研修会において、
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今野兼次郎, 畠山美香, 小川哲平, 塩谷恭子
内視鏡プロー
ブを用いたマウスへの安定・安全な気管チューブ挿管と吸
入麻酔の検討. 第60回日本日本実験動物学会総会，つくば
市，2013.5.15-17
今野兼次郎
実験動物医学専門医協会主催 The 2nd
JCLAM Forum ۱TƍŶŻƜ0º~Ēįğ®ćƊ
RefinementƒƏDJCLAMƏ<ƛéƕűŁ 2) 導入麻酔として
の三種混合麻酔（げっ歯類の気管挿管) . 第156回日本獣医
学会学術集会，岐阜市，2013.9.20-22
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⛉Ꮫ◊✲㈝ຓᡂ㔠 ᇶ┙◊✲ &㸦୍⯡㸧
ㄢ㢟ྡ㸸⏬ീᨭ᥼ᐃ఩⬻ᡭ⾡ࡢ᪂つࣔࢹࣝ☜⋡࡟ྥࡅࡓ࣑
ࢽࣈࢱࡢ⬻ᆅᅗస〇
◊✲௦⾲⪅
㰻⸨ᩄஅࠊྲྀᚓᖺᗘ㸸+㻙 ᖺ㸦㸱ᖺ㸧
◊✲ᐊ䝯䞁䝞䞊䠄䠐ᖺ⏕䠅䛸䛾㞟ྜ෗┿
⛉Ꮫ◊✲㈝ຓᡂ㔠 ᇶ┙◊✲ &㸦୍⯡㸧
ㄢ㢟ྡ㸸࢘࢖ࣝࢫᛶ⚄⤒⑌ᝈ࡟ᙳ㡪ࢆཬࡰࡍᐟ୺せᅉ࡜⎔
ቃせᅉ
◊✲௦⾲⪅
す㔝ె௨ࠊྲྀᚓᖺᗘ㸸+㻙 ᖺ㸦㸱ᖺ㸧
ຓᩍ㻌 ᰁ㇂㻌 ᱻ
⣽⳦Ꮫ◊✲ᐊ
Assist. Prof. Azusa SOMEYA, D.V.M., Ph.D.㻌
㻸㼍㼎㼛㼞㼍㼠㼛㼞㼥㻌㼛㼒㻌㻮㼍㼏㼠㼑㼞㼕㼛㼘㼛㼓㼥㻌
The prevalence of Bartonella in cattle was also
㻌
䠍䠊◊✲ᴫせ㻌
investigated.
㻌 ᚤ⏕≀䛿䛒䜙䜖䜛䛸䛣䜝䛻Ꮡᅾ䛧䛶䛚䜚䚸᫬䛻ື≀䜔ே
㻌
䛾೺ᗣ䜢⬣䛛䛩䛣䛸䜒䛒䜛䚹䛺䛛䛷䜒ື≀䛸ே䛾཮᪉䛻ឤ
䠐䠊ㄽᩥ䠈ⴭ᭩䛺䛹㻌
ᰁ䛩䜛ᚤ⏕≀䛿䚸ே䛸ື≀䛸䛾㛵䜟䜚᪉䛜ከᵝ໬䛩䜛⌧
Hirono, Y., Tanahashi, Y., Sasaki, K., Konno, K., Shirai, Y.,
௦♫఍ 䛻䛚䛔䛶䚸ே ⋇ඹ ㏻ឤ ᰁ⑕䜔㣗ရ⾨ ⏕ୖ 䛾ၥ
Kobayashi, K., Someya, A., Inaga, S., Sakura, M., Pinkerton, K.
㢟䜢ᘬ䛝㉳䛣䛩ྍ⬟ᛶ䛜䛒䜛䛯䜑䚸኱䛝䛺ὀ┠䜢㞟䜑䛶
E., Takeuchi, M.: Alveolar macrophage functions and DNA
䛔䜛䚹ᮏ◊✲ᐊ䛷䛿䚸䝬䝎䝙፹௓ᛶឤᰁ⑕䛾␿Ꮫㄪᰝ䚸
damage in cigarette smoke-exposed mice. Adv. Biosci. and
㣗⫗䛾ὶ㏻⌧ሙ䛻䛚䛡䜛኱⭠⳦䛾ᢠ⳦⸆⪏ᛶ䚸䜴䝅䛾
Biotechnol. 4:1-7 (2013)
⾑ᾮ䛻ឤᰁ䛩䜛䝞䝹䝖䝛䝷䛻䛴䛔䛶◊✲䛧䛶䛔䜛䚹㻌
ᰁ㇂ᱻ䚸ụỌ඘ᏹ䚸኱すಟ䚸Igor Velado Fernandez䚸す㔝ె௨䚸
㻌
๓⏣⛅ᙪ䠖ி㒔ᕷᒣ⛉༊䛷㥑㝖䛥䜜䛯䜲䝜䝅䝅䛻ᐤ⏕䛧䛶䛔䛯
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
䝬䝎䝙㢮䛾ゎᯒ䠊ி㒔⏘ᴗ኱Ꮫ⥲ྜᏛ⾡◊✲ᡤᡤሗ
㻌 䝬䝎䝙䜔䝜䝭䛺䛹䛾྾⾑ᛶ䛾⠇㊊ື≀䛿䚸䝠䝖䛸ື≀䛾
8:57-62
཮᪉䛻ᐤ⏕䛩䜛䛣䛸䛛䜙䚸䛥䜎䛦䜎䛺ே⋇ඹ㏻ឤᰁ⑕䜢
ᰁ㇂ᱻ䠖䝸䜿䝑䝏䜰䚸䜽䝷䝭䝆䜰䠊 ື≀ᚤ⏕≀Ꮫ᳨ᰝᏛ㻌 䠄༳ๅ୰䠅
፹௓䛩䜛ྍ⬟ᛶ䛜䛒䜛䚹௒ᖺᗘ䛿䚸ி㒔ᕷ䛻䛚䛡䜛䝬䝎
㻌
䝙䛾ศᕸ䜢䜘䜚ヲ⣽䛻᫂䜙䛛䛻䛩䜛䛯䜑䚸ẖ㐌 㻝 ᅇ䝬䝎
䠑䠊Ꮫ఍Ⓨ⾲䛺䛹㻌
䝙䛾᥇㞟䜢⾜䛔䚸䝬䝎䝙䛾Ꮨ⠇ᾘ㛗䜢᫂䜙䛛䛻䛧䛯䚹䜎
ఀ⸨ளᕼ䚸⡿ᓥ୓᭷Ꮚ䚸Igor Velado Fernandez䚸⚟⏣⨾ᶞ䚸ᰁ
䛯䚸䝬䝎䝙䛻ឤᰁ䛧䚸᪥ᮏ⣚ᩬ⇕䜢ᘬ䛝㉳䛣䛩 㻾㼕㼏㼗㼑㼠㼠㼟㼕㼍㻌
㇂ᱻ䚸๓⏣⛅ᙪ䠖ி㒔ᕷ䛻䛚䛡䜛⺅፹௓ᛶ䝣䝷䝡䜴䜲䝹䝇፹௓
㼖㼍㼜㼛㼚㼕㼏㼍 䛾ಖ᭷≧ἣ䜢ㄪᰝ䛧䛯䚹䛭䛾⤖ᯝ䚸䝬䝎䝙䛾✀
⺅䛾ㄪᰝ䠊➨48ᅇ᪥ᮏ⬻⅖䜴䜲䝹䝇⏕ែᏛ◊✲఍䠈⇕ᾏᕷ䠈
䛻䜘䜚䚸䝸䜿䝑䝏䜰䛾ಖ᭷⋡䛜␗䛺䜛䛣䛸䛜᫂䜙䛛䛻䛺䛳䛯䚹
2013.5.24-25
䛥䜙䛻䚸㣗⫗䛾ὶ㏻⌧ሙ䜘䜚኱⭠⳦䜢ศ㞳䛧䚸⸆๣ឤཷ
ᛶ䛾ㄪᰝ䜢⾜䛳䛯䚹䜎䛯䚸䜴䝅䛾⾑ᾮ䜢᥇ྲྀ䛧䚸䝞䝹䝖䝛
䠒䠊䛭䛾௚≉グ஦㡯㻌
䝷䛾ឤᰁ≧ἣ䜢ㄪᰝ䛧䛯䚹 㻌
䠍䠅㻌 እ㒊㈨㔠
㻌
ி㒔⏘ᴗ኱Ꮫ䞉≉ᐃㄢ㢟◊✲㻌
㸱㸬Research projects and annual reports
ㄢ㢟ྡ䠖䛂ி㒔ᕷ䛾ឤᰁ⑕䛾␿Ꮫⓗゎᯒ䛸ឤᰁ⑕䝬䝑䝥䛾స
〇䛃䛻㛵䛩䜛ᇶ┙◊✲㻌
The microorganism exists in all places, and might
◊✲ศᢸ⪅䠖ᰁ㇂ᱻ㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻠㻙㻞㻡 ᖺ㻌 㻔㻞 ᖺ㻕㻌
threaten human and animal health. Zoonotic and food
poisoning microorganism which can infect both animals
䠎䠅▱㈈ᶒ➼㻌
and humans cause concern for public health.
ᰁ㇂ᱻ䠖䜴䜲䝹䝇୙ά໬๣䚸ᢠ⳦๣䚸䜴䜲䝹䝇୙ά໬᪉ἲ䚸୪
䜃䛻䚸ᢠ⳦᪉ἲ䠊≉㢪 㻞㻜㻝㻟㻙㻝㻝㻜㻤㻠㻥㻌
Arthropods can transmit zoonotic pathogens such as
spotted fever group rickettsiae. Rickettsia japonica, the
䠏䠅Ꮫእάື㻌 㻌
etiological agent of Japanese spotted fever is also
ᰁ㇂ᱻ䠖ி㒔ᕷ⾨⏕⎔ቃ◊✲ᡤ䛸䛾ඹྠ◊✲㻌
associated with arthropod vector, mainly ticks. Therefore,
ᰁ㇂ᱻ䠖኱㜰ᗓ❧኱Ꮫᐈဨ◊✲ဨ㻌
the prevalence of ticks in Kyoto was investigated. Ticks
䠐䠅䛭䛾௚㻌 䛺䛧㻌
were collected weekly by flagging method and rickettsial
㻌
DNA was detected by PCR. The rate of rickettsial
infection depended on tick species.
The drug resistant bacterium in food processing can
spread the drug resistance to commensal microflora in
human. Therefore, susceptibility to antimicrobials in
Escherichia coli isolated from slaughterhouse was
investigated.
Assoc. Prof. Hiroki Takakuwa, D.V.M., Ph.D.Ď
!"#)*",)*.)& (&%$,')-+'+%"+% 54
3: Development of strategies for the prevention and
Ď ©:ğ®IJČʼnŲŢŮŌŲŔŊʼnŮŗĵĴķxÕų
control of the infections.
Õ g † ² ķ´ ª ĨB v ? 1 īńıĦłğ ņ0 ļ#
Due to concerns that wild birds could possibly spread
¤ĶÛKņľįŁĬıĦłğg†²ķ'6IJģѱ'
H5N1 viruses, surveillance was conducted to monitor the
ķªhņß{ĬğœŲśŰŴŮĭŃĪijĸöÞĵáćIJģ
types of avian influenza viruses circulating among the
ŃĠĎ
wild birds migrating to or inhabiting in northern Vietnam.
ŸŶČʼnŲŢŮŌŲŔŊʼnŮŗĵĴķ±'ķÔ£®IJķ
An H5N2 virus isolated from a Eurasian woodcock had a
GÍijñ$ĦŀĹsŒņß{ĭŃĠĎ
close phylogenetic relationship to H5 viruses recently
ŹŶMij±'ķ¸¬ņ߂Ĭğ±'ķM=
isolated in South Korea and Japan, suggesting that H5N2
ņ–JĭŃ6Fğ±'dķ´©ŒğMķ°cÆ
has been shared between Vietnam, South Korea, and
ķß{ņØĥĠĎ
Japan. An H9N2 virus isolated from a Chinese Hwamei
źŶg†²ķàwğĀij—³™ķû´ņØĤğ#¤ijŠ
was closely related to two H9N2 viruses that were
śķg†²ņĀų
isolated from humans in Hong Kong, suggesting that an
9ĭŃĠĎ
Ď
H9N2 strain relevant to the human isolates had been
642
transmitted to and maintained among the wild bird
Ď ĝĘĞĔ <ċ±'dČʼnŲŢŮŌŲŔķ´ª;=IJģ
population in Vietnam and South China. The results
ŃťśŜũĶĦĤığªeĦŀĹĈ€ĭŃ,Á÷ČüIJ
support the idea that wild bird species play a significant
Î o īńıĤŃČ ʼnŲŢŮŌŲŔŊʼnŮŗķ Ÿ ⠇ ņ
role in the spread.
ØİįĠĮķ˄ğūŨŕŐħŁąīńį ĝĘĞĕ <
Ď
ČʼnŲŢŮŌŲŔŊʼnŮŗĨî[ňŖňķąˆijî
74310
ÐIJģłğĝĘĞĕ <ŊʼnŮŗĸĪńŁķ;=Îoīńı
K. Hotta, H. Takakuwa, T. Yabuta, T. T. Ung, T. Usui, H. L.
ĤŃ+ÓdĨģŃĠĻįğŎšřŬŊħŁąīńį ĝěĞĕ
Nguyen, T. T. Le, M. Q. Le, T. Yamaguchi, K. Otsuki, T. Ito, T.
<ČʼnŲŢŮŌŲŔŊʼnŮŗĸğĮķağĊ ķŠśħ
Murase, T. Yamashiro. Antibody survey on avian influenza
ŁąīńįˆijòFd¥ĨĆYĶîÐIJģİįĪij
viruses using egg yolks of ducks in Hanoi between 2010 and
ħŁğťśŜũĿ7ĶĦĤığ÷ČķüIJŊʼnŮŗĨÎ
o īńğŠśķü IJķx įĵČ ʼnŲŢŮŌŲŔŊʼnŮŗķ
2012. Veterinary microbiology. 2013. 166, 179-183
H. Takakuwa, T. Yamashiro, M. Q. Le, L. S. Phuong, H. Ozaki, R.
›ØĶ÷ČĨýŅİıĤŃ+Ódņ½3ĬıĤįĠĎ
Tsunekuni, T. Usui, H. Ito,T. Yamaguchi, T. Ito, T. Murase, E.
Ď
Ono, K . Otsuki. The characterization of low pathogenic avian
Research projects and annual reports
Currently,
outbreaks
of
highly
pathogenic
influenza viruses isolated from wild birds in northern Vietnam
avian
from 2006 to 2009. Comparative immunology, microbiology
influenza and other emerging and re-emerging diseases
have caused serious economical and social disturbances
and infectious diseases. 2013. 36, 581-590
Y. Fujimoto, K. Ozaki, M. Maeda, K. Nishijima, H. Takakuwa, K.
worldwide. To control these infections is the most
Otsuki, H. Kida, E. Ono. Resistance to influenza A virus
important. Our research is focused on:
infection in transformed cell lines expressing an anti-PB2
1: The evolution and spread mechanism of pathogens
monoclonal antibody. Veterinary journal. 2013. 198, 487-493
such as avian influenza virus in nature.
Ď
2: Studies on the host range determinant in pathogens,
8410Ď
mechanisms of pathogenesis and immune response of the
H. Takakuwa, K. Hotta, T. Yamashiro, M. Q. Le, L. S. Phuong, T.
hosts through in vivo and in vitro analyses of the
Usui, H. Ozaki, H. Ito, T. Murase, T. Yamaguchi, T. Ito, E.
host-parasite interactions.
Ono, K. Otsuki: Distribution of antibodies to Influenza Virus in
Wild Birds in Northern Vietnam in 2011. Asia-Africa Research
Forum on Emerging and Reemerging Infections 2013, Tokyo,
2013.1.23-24
K. Hotta, H. Takakuwa, T. Yabuta, T. T. H. Ung, N. L. K. Hang,
ċ‰`Žìƒ•«¹ų
‹rñä
ġ
ž”y™ķû´ĢAõOúLĎ
L. T. Thanh, L. Q. Mai, K. Otsuki, T. Ito, T. Murase, T.
ŻŶĎ )éÅĎ ĵĬĎ
Yamashiro: Antibody Survey on Avian Influenza Viruses using
żŶĎ ĮķĎ ĵĬĎ
Duck’s Egg Yolk in Hanoi, during 2010 to 2012. Asia-Africa
Research Forum on Emerging and Reemerging Infections 2013,
Tokyo, 2013.1.23-24
ċ‰`:ťśŜũĶĦĩŃČʼnŲŢŮŌŲŔŊʼnŮŗ¢¥˜.
Zi24[]z§%X§%HÙH[‘Cųz«‹
#¤§%HŕŲŧŖŊũġČʼnŲŢŮŌŲŔŊʼnŮŗķ}î
ķ#/Ģ, CÿW, 2013.2.9-11.
×ğQUÌğ!­ă`ğÝTãğċ‰`ğC
ğ4­IğP÷fô: lPB2ÉÒ´©&őŰŴŲlķ
A<ʼnŲŢŮŌŲŔŊʼnŮŗĶNĭŃg†mld. Ä1565z
§%HHÙĄ, SþW, 2013,9,20-22
×ğQUÌğċ‰`ğP÷fô: +¡<şőřŲ2Ķ
ŀŃ&ÈŤŮŦŗŊʼnŮŗ2< ĶNĭŃüqµg†mldķ
. Ä615zŊʼnŮŗHHÙĄŷ¾jWŷ
2013.11.10-12
Ď
94/2
ŸŶĎ Aõèø
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á ć . ŽČ ʼnŲŢŮŌŲŔŊʼnŮŗķč ĺķg † d ¨ b Ūō
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áć.ŽŏŞůŝŲÊêýðòFt@ŨŊŗĶŀх¾
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ŹŶĎ ºæŽÅĎ Ď
ûzŽĕēĔĖ [ Ě ~ ĔĔ zĎ
.ÀŽČʼnŲŢŮŌŲŔŊʼnŮŗĶNĭў”y™Ď
´{ÑŽCğċ‰`ğY8ÖDğV*·^ğ'óEğ
C¦Eğœ—Ď
źŶĎ HAš#Ď Ď
ᩍᤵ㻌 ➉ෆ㻌 ᐇ
ච␿⑓⌮Ꮫ◊✲ᐊ
Prof. Minoru Takeuchi, Ph.D., D.V.M., M.Sci.D.㻌
㻸㼍㼎㼛㼞㼍㼠㼛㼞㼥㻌㼛㼒㻌㻵㼙㼙㼡㼚㼛㼜㼍㼠㼔㼛㼘㼛㼓㼥
㻌
䠍 䠊◊✲ᴫせ㻌
㻸㻼㻿 䛻䜘䜛⫵ච␿⣽⬊䜈䛾ᙳ㡪䛻䛴䛔䛶◊✲䛧䛶䛔䜛䚹
㻌 ⎔ቃศ㔝䛷㔜せ䛺ၥ㢟䛸䛧䛶ྲྀ䜚ୖ䛢䜙䜜䛶䛔䜛䝍䝞
䜎䛯䚸⫵䛻ᙳ㡪䜢୚䛘䚸䜰䝺䝹䜼䞊䜢Ⓨ⑕䛥䛫䜛䛣䛸䛷▱
䝁ႚ↮䛻╔┠䛧䚸ႚ↮䛾ච␿䚸⒴ቑṪ䞉㌿⛣䚸㻰㻺㻭 ᦆയ
䜙䜜䛶䛔䜛䝇䜼ⰼ⢊䛜䛒䜛䚹᪥ᮏ䝇䜼ⰼ⢊䠄 㻯㼞㼥㼜㼠㼛㼙㼑㼞㼕㼍㻌
䜈䛾ᙳ㡪䛻䛴䛔䛶䚸䝬䜴䝇䜢⏝䛔䛶◊✲䛧䛶䛔䜛䚹ႚ↮䛸
㼖㼍㼜㼛㼚㼕㼏㼍㻌 㼜㼛㼘㼘㼑㼚䠅䛿䚸䜹䜼≧䛾✺㉳䠄䝟䝢䝷䠅䜢᭷䛩䜛༢⢏
ච␿䛸⒴䛿䚸䛭䜜䛮䜜ᐦ᥋䛻㛵ಀ䛧䛶䛚䜚䚸䛣䜜䜙䛾㛵
⌫ᙧ䛾ᙧ≧䛷䚸㻵 ᆺ䛾㐣ᩄ⑕䜢ᘬ䛝㉳䛣䛩䛣䛸䛷▱䜙䜜䛶
ಀ䜢ゎ᫂䛩䜛䛣䛸䛿኱ኚព⩏䛜䛒䜛䚹䛣䜜䜎䛷䛾◊✲䛷䚸
䛔䜛䚹䛧䛛䛧䚸䝇䜼ⰼ⢊䛸䛭䛾ᡂศ䛜⏕య䛻྾ධ䛥䜜䛶䛛
䝍䝞䝁ႚ↮ 䛻䜘䜚⫵ ⬊䝬䜽䝻䝣䜯䞊䝆䛾㈎㣗⬟䚸ᢠཎᥦ
䜙䛾⫵ච␿⣔䛻ཬ䜌䛩ᙳ㡪䛻䛴䛔䛶䛿༑ศ䛺ゎ᫂䛿䛥
♧⬟䚸⣽⬊⾲㠃ᢠཎ䚸䝃䜲䝖䜹䜲䞁 㼙㻾㻺㻭 Ⓨ⌧䛺䛹䛾ච
䜜䛶䛔䛺䛔䛯䜑䚸䝇䜼ⰼ⢊䛻䜘䜛⫵䛾ึᮇච␿ᛂ⟅཯ᛂ
␿ᶵ⬟䛿ᢚไ䛥䜜䛶䛔䜛䛜䚸㏫䛻άᛶ㓟⣲䛾⏘⏕⬟䛿
䛻䛴䛔䛶䜒◊✲䜢䛧䛶䛔䜛䚹㻌
ቑຍ䛩䜛䚹䛭䛣䛷⌧ᅾ䛿䚸ႚ↮䛻䜘䜚ቑຍ䛧䛯άᛶ㓟⣲
䠏䠅ኳ↛ᡂศ䛾ච␿స⏝䛸䛭䛾ᛂ⏝䛻䛴䛔䛶㻌
䛻䜘䜚䚸⫵⬊䝬䜽䝻䝣䜯䞊䝆䛚䜘䜃⫵⤌⧊䛾 㻰㻺㻭 ᦆയ䛜
䐟⻏⻤㻌
ㄏᑟ䛥䜜䚸䛭䛾⤖ᯝ␗ᖖ 㻰㻺㻭 䛜ᙧᡂ䛥䜜䚸⫵⒴䛾Ⓨ⏕
ኳ↛ᡂศ䛻䛿ᵝ䚻䛺⏕⌮άᛶ䛜▱䜙䜜䛶䛚䜚䚸⻏⻤
䛻䛣䜜䜙䛾せᅉ䛸పୗ䛧䛯ච␿ᶵᵓ䛜㛵ಀ䛧䛶䛔䜛ྍ⬟
䛿䚸ᰤ㣴䛜㇏ᐩ䛺ኳ↛䛾㣗ရ䛸䛧䛶ぶ䛧䜎䜜䛶䛔䜛䚹⻏
ᛶ䛻䛴䛔䛶◊✲䛧䛶䛔䜛䚹䜎䛯ᢚไ䛥䜜䛯ච␿ᶵ⬟䜢ᅇ
⻤䛾䜂䛸䛴䛷䛒䜛䝆䝱䞁䜾䝹䝝䝙䞊䛿䚸䜰䝣䝸䜹䞉䝘䜲䝆䜵
᚟䛩䜛䛯䜑䛻䚸ኳ↛ᡂศ䠄䜰䜺䝸䜽䝇Ⲗ䚸⻏⻤䠅䛾ච␿ቑ
䝸䜰䛾⇕ᖏ㞵ᯘ䛻⏕ᜥ䛩䜛㔝 ⏕䛾⻤⻏䛜㛗ᮇ䛻䜟䛯䜚
ᙉస⏝䛻䛴䛔䛶◊✲䛧䚸᪂⸆䛾㛤Ⓨ䜢┠ᣦ䛧䚸䛂ႚ↮䛸
ᶞᮌ䜔ⰼ䛛䜙㞟䜑䛶䛷䛝䛯⻏⻤䛷䛒䜛䚹䝘䜲䝆䜵䝸䜰䛷䛿䚸
ච␿䛸⒴䛸ኳ↛ᡂศ䜢⛉Ꮫ䛃䛧䚸௨ୗ䛾◊✲䝔䞊䝬䛻䛴
䛣䛾⻏⻤䛜㢼㑧䚸⓶⭵⅖䚸ⅆയ䛾἞⒪⸆䚸⑌ᝈண㜵⸆
䛔䛶◊✲䜢㐍䜑䛶䛔䜛䚹㻌
䛸䛧䛶ఏ⤫ⓗ䛺་⒪䛻฼⏝䛥䜜䛶䛝䛯䚹䛭䛾䛯䜑㣗⏝䛷
䠍䠅䝍䝞䝁↮䛻䜘䜛⫵⬊䝬䜽䝻䝣䜯䞊䝆䜈䛾ᙳ㡪䛸㑇ఏᏊ
䛿䛺䛟䚸䜐䛧䜝἞⒪⸆䛸䛧䛶౑⏝䛥䜜䛶䛔䜛䛣䛸䛛䜙䚸⏕య
ᦆയ䛻䛴䛔䛶㻌
䜈䛾స⏝䚸≉䛻ච␿స⏝䛻ᑐ䛩䜛ຠᯝ䛜⪃䛘䜙䜜䜛䚹䛭
䝍䝞䝁ႚ↮ 䛻䜘䜚䚸䝍䝞䝁
䛣䛷䚸䝆䝱䞁䜾䝹䝝䝙䞊䛾ච␿ᶵ⬟䜈䛾ᙳ㡪䛸䛭䛾స⏝
↮䛿┤᥋⫵䛻྾ධ䛥䜜䜛䛯
ᶵᵓ䚸ᢠ⭘⒆స⏝䛻䛴䛔䛶◊✲䜢䛧䛶䛔䜛䚹䜎䛯䚸᪥ᮏ
䜑䚸⫵䛻Ꮡᅾ䛩䜛ච␿⣽⬊
඲ᅜ䛛䜙⻤※䛾㐪䛖᪥ᮏᅜ⏘䝝䝏䝭䝒䛾ච␿ᶵ⬟䜈䛾
䜔⫵⤌ ⧊䜈䛾ᙳ㡪 䛜䛒䜛䛸
ᙳ㡪䛸᭷ຠᡂศ䛻䛴䛔䛶䜒◊✲䜢㛤ጞ䛧䛶䛔䜛䚹㻌
⪃ 䛘 䜙䜜䜛䚹 ≉ 䛻⫵ 䛾ච ␿
䐠䜰䜺䝸䜽䝇Ⲗ㻌
⣔䛷୰ᚰⓗ䛺ᙺ๭䜢ᢸ䛳䛶
䜰䜺䝸䜽䝇䛿䚸Ꮫྡ䛂䜰䜺䝸䜽䝇䝤䝷䝊䜲䝮䝸䝹䠄㻭㼓㼍㼞㼕㼏㼡㼟㻌
䛔䜛⫵⬊䝬䜽䝻䝣䜯䞊䝆䛾ᶵ
㼎㼘㼍㼦㼑㼕㻌 㻹㼡㼞㼕㼘㼘䠅䛃䚸࿴ྡ䜢䛂䜹䝽䝸䝝䝷䝍䜿䛃䛸䛔䛖㣗⏝䜻䝜䝁
⬟䛻ᑐ 䛩䜛䝍䝞䝁ႚ↮ 䛾ᙳ
䛷䚸䝤䝷䝆䝹䛾䝢䜶䝎䞊
㡪䜢ㄪ䜉䜛䛣䛸䛿䚸⫵䛾ච␿
䝔ᆅ᪉䛸࿧䜀䜜䜛㧗ᆅ䛻
⣔䚸䜂䛔䛶䛿⏕య㜵ᚚ䜢⪃
၏ ୍ ⮬ ⏕ 䛧 䛶 䛔 䜛䚹 䛣 䛾
䛘䜛ୖ䛷㔜せ䛷䛒䜛䚹䛭䛣䛷䚸⮬ືႚ↮⿦⨨䜢⏝䛔䛶䚸
ᆅ䛷ᬽ䜙䛩ே䚻䛜᫇䛛䜙
䝬䜴䝇䛻୍ᐃ㔞䚸୍ᐃᮇ㛫䚸ᆒ୍䛻䝍䝞䝁↮䜢ႚ↮䛥䛫
㣗⏝䛻䛧䛶䛝䛯䜻䝜䝁䛷䛒
䛯ᚋ䚸Ẽ⟶ᨭ⫵⬊Ὑί䛻䜘䜚⫵⬊䝬䜽䝻䝣䜯䞊䝆䜢᥇ྲྀ
䜛䚹䝢䜶䝎䞊䝔ᆅ ᪉ 䛾ཎ
䛧䚸⫵⬊䝬䜽䝻䝣䜯䞊䝆䛾ච␿ᶵ⬟䛸㑇ఏᏊ䜈䛾ᙳ㡪䛚
ఫ Ẹ 䛻 䛿⏕ ά ⩦ ័ ⑓ 䛾
䜘䜃ႚ↮䛾 㻸㻼㻿 ⫵⅖⑕䜈䛾ᙳ㡪䚸䝇䜼ⰼ⢊䛻䜘䜛⫵䜈
ᝈ⪅䛜ᑡ䛺䛟㛗ᑑ⪅䛜ከ䛔䛣䛸䛛䜙◊✲䛜㐍䜑䜙䜜䚸䜰
䛾ᙳ㡪䛻䛴䛔䛶䜒◊✲䛧䛶䛔䜛䚹㻌
䜺䝸䜽䝇䛻䛿ච␿άᛶ䛜▱䜙䜜䛶䛔䜛䚹䛧䛛䛧䚸ච␿స⏝
䠎䠅㻸㻼㻿 䛚䜘䜃䝇䜼ⰼ⢊䛾ึᮇච␿ᛂ⟅䛻䛴䛔䛶㻌
䛾ᶵᵓ䛻䛴䛔䛶䛿༑ศ䛻ゎ᫂䛥䜜䛶䛔䛺䛔䛯䜑䚸䛭䛾䝯
䜾 䝷 䝮 㝜 ᛶ ⳦ ⏤ ᮶ 䛾 ෆ ẘ ⣲ 䛷 䛒 䜛
䜹䝙䝈䝮䛸᭷ຠᡂศ䛻䛴䛔䛶◊✲䛧䛶䛔䜛䚹㻌
㻸㼕㼜㼛㼜㼛㼘㼥㼟㼟㼍㼏㼏㼔㼍㼞㼕㼐㼑㻌 㻔㻸㻼㻿㻕䛿䚸ᵝ䚻䛺ච␿άᛶ䜢᭷䛧䚸
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
䝍䝞䝁↮䜔⎔ቃ୰䛻ྵ䜎䜜䛶䛚䜚䚸࿧྾䜔ႚ↮䛻䜘䜚⫵
㻌 ႚ↮䛾⫵ච␿⣔䜈䛾ᙳ㡪䛻䛴䛔䛶䛿䚸⫵⬊䝬䜽䝻䝣䜯
䛻྾ධ䛩䜛䛣䛸䛻䜘䜚⫵⬊㡿ᇦ䛻ྲྀ䜚㎸䜎䜜䜛䚹䛭䛣䛷䚸
䞊䝆䛾ᢠཎᥦ♧ᶵ⬟䛾ᢚไ䛜ㄆ䜑䜙䜜䛯䚹䛣䛾ᢚไᶵ
ᵓ䛻䛴䛔䛶䛿䚸㻭㻹 䛜䝍䝞䝁⢏Ꮚ䜢⣽⬊㉁ෆ䛻ྲྀ䜚㎸䜏䚸
smoking.” Since the fact that immune functions are
⣽⬊ෆ㒊ᵓ㐀䜢」㞧໬䛥䛫䚸⣽⬊⬊య䛾䝃䜲䝈䜒ቑຍ
suppressed by smoking and tumor growth, we are also
䛧䚸✵⬊ኚᛶ䛜ㄆ䜑䜙䜜䚸䛭䛾⤖ᯝ䚸⣽⬊ෆ䛻ᑒධయ䜢
investigating
ᙧᡂ䛧䛶䛔䜛䛣䛸䛜㟁Ꮚ㢧ᚤ㙾䛻䜘䜚☜ㄆ䛥䜜䚸䛣䛾 㻭㻹
restoration of suppressed immune functions by natural
䛾⣽⬊ෆኚ໬䛜䚸㻭㻹 䛾ච␿ᶵ⬟䛾ᢚไ䛻㛵ಀ䛧䛶䛔
products.
䜛䛣䛸䛜♧䛥䜜䛯䚹㻌
1: Study for tobacco smoke
the
mechanisms
of
inhibition
and
ኳ↛ᡂศ䛻㛵䛧䛶䛿䚸᪥ᮏᅜ⏘䝝䝏䝭䝒䛻䛿⫵⬊䝬䜽
Cigarette smoke is a major risk factor for pulmonary
䝻䝣䜯䞊䝆䜢άᛶ໬䛥䛫䚸ዲ୰⌫䛻ᑐ䛩䜛⛣ືᛶ䞉㉮໬
diseases. Cigarette tobacco smoke particles are inhaled
άᛶ䛜᪂䛧䛟ㄆ䜑䜙䜜䚸䜎䛯䝆䝱䞁䜾䝹䝝䝙䞊䛻ᢠయ ⏘
into the lung and reach alveolar space, and then directly
⏕ᶵ⬟䜢ቑᙉ䛩䜛䛣䛸䛜᪂䛧䛟ㄆ䜑䜙䜜䚸⣽⳦ឤᰁ䛻᭷
encounter Alveolar Macrophages (AM). Smoking has
ຠ䛷䛒䜛䛣䛸䛜♧၀䛥䜜䛯䚹䜎䛯䚸䜰䜺䝸䜽䝇Ⲗ⇕Ỉᢳฟ
been shown to increase production of reactive oxygen by
ᾮ䜒ዲ୰⌫䛾㐠ືᛶ䜢ஹ㐍䛧䚸⛣ື᪉ྥᛶ䜢㧗䜑䚸⛣
alveolar macrophages, which induce DNA damage in
ື㏿ᗘ䜢㏿䜑䜛䛣䛸䛜ド᫂䛥䜜䛯䚹䛥䜙䛻䚸䜰䜺䝸䜽䝇䛿䚸
these cells, and it has also been demonstrated that their
ᶵ⬟పୗ䛧䛯ዲ୰⌫䛾㈎㣗ᶵ⬟䜢ᅇ᚟䛥䛫䜛䛣䛸䜒ド᫂
immune functions such as antigen presentation and
䛥䜜䚸䛣䜜䜙䛾ኳ↛ᡂศ≀㉁䛿䚸⣽⳦䜈䛾⛣ືᛶ䜢᪩䜑䚸
cytokine production are impaired. Inclusion bodies of
㈎㣗స⏝䜢㧗䜑䚸ዲ୰⌫ᶵ⬟䜢άᛶ໬䛧䚸⣽⳦ឤᰁ䜢
high density appeared in the cytoplasm of AM by
㜵ᚚ䛩䜛ྍ⬟ᛶ䛜♧၀䛥䜜䛯䚹㻌
cigarette smoke..
䝇䜼ⰼ⢊㻔㻯㻶㼜㻕䛻䜘䜛⫵䛾ึᮇච␿ᛂ⟅䛻㛵䛧䛶䛿䚸
2: Study for Natural products
䝇䜼ⰼ⢊䛾Ẽ⟶ᨭෆ ᢞ୚䛻䜘䜚䚸⫵ẟ⣽⾑⟶ 䛛䜙ዲ ୰
(1) Honey
⌫䛾⫵㛫㉁䚸⫵⬊⭍ 䜈䛾ὶ ධ䛜
Natural products are known to have biological activity,
ㄆ䜑䜙䜜䚸ᛴᛶ⫵⅖⑕䛜ᘬ䛝㉳䛣
and we have previously investigated the effect of natural
䛥䜜䛯䚹ዲ ୰ ⌫ 䛾⫵ 䜈 䛾ㄏ ᑟ ᶵ
products on immune function. Honey contains various
ᵓ䛸䛧䛶䛿䚸䝇䜼ⰼ⢊䛾 㻯㼞㼥㼖㻝 䛻
vitamins, minerals and amino acids as well as glucose
ዲ ୰ ⌫ 䛻ᑐ 䛩䜛㉮ ໬ ά ᛶ 䛜䛒䜛
and fructose and is popular as a natural food. There is a
䛣䛸䛜ㄆ䜑䜙䜜䚸䜎䛯 㻯㻶㼜 䛜⫵⬊
wide variety of honey and the varieties are due to
䝬䜽䝻䝣䜯䞊䝆䛾 㼀㻸㻾㻠 䛷䛿䛺䛟
components of flower sources. Jungle honey is used as
㼀㻸㻾㻞 䜢 ௓ 䛧 䛶 ่ ⃭ ᚋ 䚸 ዲ ୰ ⌫ 䛾 䜿 䝰 䜹 䜲 䞁 䛷 䛒 䜛
traditional medicine for cold, skin inflammation and
㻯㼄㻯㻸㻞 䛾⏘⏕ቑᙉ䛻䜘䜛䛣䛸䛜ゎ᫂䛥䜜䛯䚹㻌
burn wound but not only health care. JH enhanced
㻌
antibody production through the increase of CD19
㸱 㸬Research projects and annual reports
positive cells and proliferation of spleen cells by
We are focusing on cigarette smoke, which is currently
augmentation of IL-1β and IL-6 mRNA expressions.
mRNA expressions in
attracting attentions as an environmental problem. The
Japanese honey enhanced IL-1β
World Health Organization (WHO) reports that mortality
alveolar macrophage.
from pulmonary diseases associated with exposure to
(2) Agaricus Blazei Murill
cigarette smoke including respiratory infections, chronic
Agaricus blazei Murill has been traditionally used as
obstructive pulmonary disease (COPD) and lung cancers,
medicine in Brazil. Agaricus blazei Murill has been
has increased. It has been suggested that these diseases
reported for anti-tumor activity and immune activity. It is
may
cigarette
unclear how Agaricus blazei Murill hot water extract
smoke-induced impairment of the pulmonary immune
be
at
least
partially
related
to
activates the immune system and anti-tumor activity.
system. Cigarette smoke is a major risk factor for
Therefore, we are focusing on the mechanism of activity
pulmonary diseases. Cigarette tobacco smoke particles
of immune functions in immune cells associated with
are inhaled into the lung and reach alveolar space, and
anti-tumor activity by Agaricus blazei Murill hot water
then directly encounter Alveolar Macrophages (AM).
extract and its characterization of effective component.
AM plays an important role as the first line of defense in
We have demonstrated that extract of Agaricus blazei
immunological surveillance for the lung. In the aim of
Murill activated immune functions neutrophils and
our study, we are investigating
macrophages in mice.
“making a science for
䠐 䠊ㄽᩥ䠈ⴭ᭩䛺䛹㻌
M. Takeuchi, Y. Hirono, M. Nose, S. Inoue, K. Sasaki, K.E.
㔜ྜྷ⍛㔛,➉ෆᐇ:ࢪࣕࣥࢢࣝࣁࢽ࣮࡟ࡼࡿᢠయ⏘⏕ᶵ⬟࡬
Pinkerton: Cigarette smoke as environmental factor induce
ࡢᙳ㡪࡜ࡑࡢᶵᵓ࡟ࡘ࠸࡚. ி㒔⏘ᴗ኱Ꮫㄽ㞟 ⮬↛⛉Ꮫ
inhibition of immune functions and DNA damage in alveolar
⣔ิ , 42, 21-52
macrophages. EAACI-WAO Congress, Milan, 2013.06.22-26
M. Miyagawa, Y. Hirono, A. Kawazoe, E. Shigeyoshi, M. Nose,
➉ ෆ ᐇ : 䝝䝏 䝭 䝒 䛸ච ␿ . ி 㒔 ⏘ ᴗ ኱ Ꮫ ᩍ 㣴 ㅮ ᗙ , ி 㒔 ᕷ ,
2013.7.6 䠄ᣍᚅㅮ₇䠅
M. Sakura, K.E. Pinkerton, M. Takeuchi: Effect of hot water
extract
from agaricus blazei
murill on
chemotaxis of
➉ෆᐇ: 䝝䝏䝭䝒䛸ච␿. ி㒔⏘ᴗ኱Ꮫ䝭䝒䝞䝏ㅮᗙ, ⟪㠃ᕷ,
neutrophils. Journal of Cosmetics, Dermatological Sciences
and Applications, 3, 12-17
2013.9.14 䠄ᣍᚅㅮ₇䠅
M. Takeuchi, Y. Hirono, M. Sakura: Cigarette smoke induces
M. Sakura, Y. Chiba, E. Kamiya, A. Furukawa, N. Kawamura, M.
DNA damage and inhibition of function in alveolar macrophage.
Niwa, M. Takeuchi, M. Hosokawa: Spontaneous occurrence of
44th Union World Conference on Lung Health, Paris,
2013.10.30- 11.3
photoaging-like phenotypes in the dorsal skin of old SAMP1
mice, an oxidative stress model. Experimental Dermatology, 22,
➉ෆᐇ: 䝝䝏䝭䝒䛸ච␿. ி㒔ᗓ⚾❧୰㧗➼Ꮫᰯ⌮⛉◊ಟ఍,
ி㒔ᕷ, 2013.11.16 䠄ᣍᚅㅮ₇䠅
62-64
Y. Hirono, A. Kawazoe, M. Nose, M. Sakura, M. Takeuchi:
➉ෆᐇ: 䝝䝏䝭䝒䛸ච␿. ி㒔ᗓ⋇་ᖌ఍⥲ྜ㒊఍◊ಟ఍, ி
㒔ᕷ, 2013.11.27 䠄ᣍᚅㅮ₇䠅
Cigarette smoke induce alteration of structure and function in
alveolar macrophages. International Journal of Bioscience,
➉ෆᐇ: WOX䛾ච␿㈿ά䛻㛵䛩䜛ຠᯝ. QOL䝃䝫䞊䝖◊✲఍,
Biochemistry and Bioinformatics, 3, 125-128
ᕝᓮᕷ, 2013.11.28 䠄ᣍᚅㅮ₇䠅
Y. Hirono, Y. Tanahashi, K. Sasaki, K. Konno, Y. Shirai, K.
Y. Hirono, K. Sasaki, Y. Tanahashi, M. Sakura, T. Ishida, S. Inaga,
Kobayashi, A. Someya, S. Inaga, M. Sakura, K.E. Pinkerton, M.
M. Takeuchi: The mechanism of inhibition of apoptosis in
Takeuchi: Alveolar macrophages functions and DNA damage in
alveolar macrophages by cigarette smoke. ➨42ᅇ᪥ᮏච␿Ꮫ
cigarette smoke-exposed mice. Journal of Advances in
Bioscience and Biotechnology, 4, 1-7
఍Ꮫ⾡㞟఍, ༓ⴥᕷ, 2013.12.11-13
K. Sasaki, Y. Hirono, Y. Tanahashi, M. Sakura, T. Ishida, M.
㻌
Takeuchi: Effect of cigarette smoking on infiltration of
䠑䠊Ꮫ఍Ⓨ⾲䛺䛹㻌
neutrophils in LPS-induced lung inflammation. ➨42ᅇ᪥ᮏච
➉ ෆ ᐇ : ⻏ ⻤ 䛾ຠ ⬟ . ᮾ ᾏ ᆅ ༊㣴 ⻏ ◊ ✲ ఍ ⥲ ఍ , ྡ ྂ ᒇ ᕷ ,
2013.1.28 䠄ᣍᚅㅮ₇䠅
␿Ꮫ఍Ꮫ⾡㞟఍, ༓ⴥᕷ, 2013.12.11-13
㻌
➉ෆᐇ: 䛿䛱䜏䛴䛻䜘䜛⏕య䛾ච␿ᶵ⬟䛻ཬ䜌䛩ຠᯝ. ᒱ㜧┴
䠒䠊䛭䛾௚≉グ஦㡯㻌
㣴 ⻏ ⤌ ྜ 㐃 ྜ ఍ タ ❧ 60 ࿘ ᖺ グ ᛕ ᘧ ඾ , ᒱ 㜧 ᕷ , 2013.2.1
䠍䠅㻌 እ㒊㈨㔠
䠄ᣍᚅㅮ₇䠅
⛉Ꮫ◊✲㈝⿵ຓ㔠䞉ᇶ┙◊✲䠄㻯䠅㻌
➉ෆᐇ: 䝝䝏䝭䝒䛜ච␿ᶵᵓ䛻ཬ䜌䛩ຠᯝ䛻䛴䛔䛶. ி㒔ᗓ㣴
ㄢ㢟ྡ䠖ཷືႚ↮䛻䜘䜛⫵⬊䝬䜽䝻䝣䜯䞊䝆䛾ᰁⰍయ␗ᖖ䛸
⻏⤌ྜ⥲఍, ⥤㒊ᕷ, 2013.2.12 䠄ᣍᚅㅮ₇䠅
㑇ఏᏊᦆയ䜈䛾ᙳ㡪㻌
◊✲௦⾲⪅䠖➉ෆᐇ㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻟㻙㻞㻡 ᖺ㻌 㻔㻟 ᖺ㻕㻌
Y. Hirono, A. Kawazoe, M. Nose, M. Sakura, M. Takeuchi:
Cigarette smoke induce alteration of structure and function in
䠎䠅㻌 Ꮫእάື㻌
alveolar
➉ෆᐇ䠖ி㒔ᗓ⋇་ᖌ఍ி㒔ᨭ㒊㛗,㻌 ி㒔ᗓᗓẸබ㛤஦ᴗ
macrophages.
3rd
International
Conference
on
᥎㐍ጤဨ,㻌Pulmonology㻌 ⦅㞟ጤဨ,㻌WJR㻌 ⦅㞟ጤဨ,㻌 䛺䛹㻌
Bioscience, Biochemistry and Bioinformatics (ICBBB 2013),
Rome, 2013.2.24-25
X. Li, M. Xue, H. Aaron, M. Tagmount, M. Takeuchi, E. Eisen, C.
䠏䠅㻌 䛭䛾௚㻌
NHK㻌 䜖䛖䛹䛝䝛䝑䝖䝽䞊䜽㻌 ㅮᖌ䛸䛧䛶ฟ₇,㻌2013.6.12
Vulpe, J. Zink, Risbud, K.E. Pinkerton: Highly mechanized
䝩䞊䝮䝨䞊䝆䜰䝗䝺䝇㻌 http://www.cc.kyoto-su.ac.jp/~mtakex/㻌
nano-structures with controlled-release targeting technology is
㻌
safe and compatible in an aerosol model for enhancing delivery.
◊✲ᐊ䝯䞁䝞䞊㻌
ATS 2013 International Conference, Philadelphia, 2013.5.17-22
M. Takeuchi, A. Kawazoe, Y. Hirono, M. Nose, S. Inaga, K.E.
Pinkerton: Effect of cigarette smoke exposure on LPS-induced
lung inflammation in mice. ATS 2013 International Conference,
Philadelphia, 2013.5.17-22
㻌㻌
⸆⌮Ꮫ◊✲ᐊ
ຓᩍ㻌 Ჴᶫ㻌 㟹⾜㻌
㻸㼍㼎㼛㼞㼍㼠㼛㼞㼥㻌㼛㼒㻌㻼㼔㼍㼞㼙㼍㼏㼛㼘㼛㼓㼥㻌
Assist Prof. Yasuyuki Tanahashi, D.V.M., Ph. D.㻌 㻌
㻌
䠍䠊◊✲ᴫせ㻌
↮䛻䜘䜚Ẽ⟶ᨭᖹ⁥➽䛾཰⦰㐣ᩄ䛜ច㉳䛥䜜䚸䛭䛾⤖
㻌 ᙜ◊✲ᐊ䛷䛿䚸୺䛻௨ୗ䛾䝔䞊䝬䛻䛴䛔䛶◊✲䜢⾜
ᯝ㉳䛣䜛Ẽ㐨䛾⊃✽䛜ཎᅉ䛾୍䛴䛸䛧䛶ᥦၐ䛥䜜䛶䛔䜛䚹
䛳䛶䛔䜛䚹㻌
䛧䛛䛧䚸ႚ↮䛜䛹䛾䜘䛖䛺䝯䜹䝙䝈䝮䛻䜘䜚Ẽ⟶ᨭᖹ⁥➽
䠄䠍䠅⭠⟶䛾㐠ືㄪ⠇ᶵᵓ㻌
䛾཰⦰㐣ᩄ䜢ᘬ䛝㉳䛣䛩䛾䛛䛻䛴䛔䛶䛿䚸䛔䜎䛰༑ศ䛻
㻌 ⭠⟶䛾㐠ື䛿䝁䝸䞁సືᛶ⚄⤒䛛䜙ᨺฟ䛥䜜䜛䜰䝉䝏
᫂䜙䛛䛻䛥䜜䛶䛔䛺䛔䚹䛭䛣䛷䚸ᮏ◊✲䛷䛿䚸⮬ືႚ↮
䝹䝁䝸䞁䛸䛭䛾ཷᐜయ䛷䛒䜛䝮䝇䜹䝸䞁ཷᐜయ䛻䜘䛳䛶⯆
⿦⨨䠄㻲㼕㼓㼡㼞㼑㻌 㻞䠅䜢⏝䛔䚸䝬䜴䝇䛻䝍䝞䝁↮䜢ᭀ㟢䛩䜛䛣䛸
ዧᛶ䛻ㄪ⠇䛥䜜䛶䛔䜛䚹䝮䝇䜹䝸䞁ཷᐜయ䛻䛿䚸䛣䜜䜎䛷
䛻䜘䜚స〇䛧䛯ႚ↮䝰䝕䝹䝬䜴
䛻䠩 䠍 䛛䜙䠩 䠑 䜎䛷䛾䠑䛴䛾䝃䝤䝍䜲䝥䛜ྠᐃ䛥䜜䛶䛚䜚䚸
䝇䜢⏝ 䛔䚸ୖ グ 䛾ᮍ ゎ Ỵ ၥ 㢟
䛣䛾䛖䛱䚸⭠⟶ᖹ⁥➽⣽⬊䛻䛿䠩 䠎 䛸䠩 䠏 䝃䝤䝍䜲䝥䛜Ꮡ
䛻ྲྀ䜚⤌䜣䛷䛔䜛䚹ᮏ◊✲䛻䜘
ᅾ䛧䛶䛔䜛䚹䝁䝸䞁సືᛶ⚄⤒䛛䜙ᨺฟ䛥䜜䛯䜰䝉䝏䝹䝁
䜚ᚓ䜙䜜䜛᝟ሗ䛿䚸ႚ↮ 䛻䜘䛳
䝸䞁䛜䛣䜜䜙䛾䝮䝇䜹䝸䞁ཷᐜయ䜢่⃭䛩䜛䛸䚸ᖹ⁥➽⣽
䛶ᘬ䛝㉳䛣䛥䜜䜛 㻯㻻㻼㻰 䛚䜘䜃
㻞㻗
⬊ෆ䛾 㻯㼍 ⃰ᗘ䛜ቑຍ䛧䚸᭱⤊ⓗ䛻➽䛿཰⦰䛩䜛䚹䜎䛯䚸
ႍᜥ䛾⑓ែゎ᫂䜔἞⒪⸆䛾
㏆ᖺ䚸⭠⟶䛾⚄⤒ྀ䛻Ꮡᅾ䛩䜛䜹䝝䞊䝹⣽⬊䠄㻵㻯㻯䠅䛸
㛤Ⓨ䛻䛚䛔䛶ከ䛟䛾ᇶ♏ ᝟ሗ
࿧䜀䜜䜛㛫㉁⣽⬊䛻䜒䝮䝇䜹䝸䞁ཷᐜయ䛜Ꮡᅾ䛧䛶䛚䜚䚸
䜢ᥦ౪䛩䜛䛣䛸䛜䛷䛝䜛䚹䛣䛾◊
⭠⟶ 䛾㐠ື ㄪ⠇ 䛻㔜せ 䛺ᙺ ๭䜢ᯝ䛯䛧䛶䛔䜛䛣䛸䛜♧
✲䛿䚸ி㒔⏘ᴗ኱Ꮫච␿⑓⌮
၀䛥䜜䛶䛔䜛䠄㻲㼕㼓㼡㼞㼑㻌 䠍䠅䚹䛧䛛䛧䚸䝁䝸䞁సືᛶ⚄⤒䛻䜘
Ꮫ ◊ ✲ ᐊ 䛸䛾ඹ ྠ ◊ ✲ 䛸 䛧䛶
䜛⭠⟶䛾㐠ືㄪ⠇䛻䛚䛔䛶䚸䠩 䠎 䚸䠩 䠏 䝃䝤䝍䜲䝥䜔䜹䝝
⾜䛳䛶䛔䜛䚹㻌
䞊䝹⣽⬊䛜䛭䜜䛮䜜䛹䛾䜘䛖䛺ᙺ๭䜢ᯝ䛯䛧䛶䛔䜛䛾䛛
㻌
➼䛾ヲ⣽䛺䝯䜹䝙䝈䝮䛻䛴䛔䛶䛿᫂䜙䛛䛻䛥䜜䛶䛔䛺䛔䚹
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
Figure 2. Hamburg
II smoking machine
䛭䛣䛷䚸ᮏ◊✲䛷䛿䚸䠩䠎 䜎䛯䛿䠩 䠏 䝃䝤䝍䜲䝥䜢Ḟᦆ䛧䛯
㻌 䠄䠍䠅⭠⟶䛾㐠ືㄪ⠇ᶵᵓ㻌
䝬䜴䝇䜔䜹䝝䞊䝹⣽⬊䜢Ḟᦆ䛧䛯䝬䜴䝇䜢⏝䛔䛶䚸ୖグ
㻌 㻌 䝁䝸䞁సືᛶ⚄⤒䛻䜘䜛ᑠ⭠⽸ື㐠ື䛾Ⓨ⌧䛻䛿䚸
䛾ᮍゎỴၥ㢟䛻ྲྀ䜚⤌䜣䛷䛔䜛䚹㻌
㻹 䠎 䝃䝤䝍䜲䝥䛜㔜せ䛷䛒䜚䚸㻹 䠏 䝃䝤䝍䜲䝥䛚䜘䜃䜹䝝䞊
䝹⣽⬊䛿䚸䜐䛧䜝Ⓨ⏕䛧䛯⽸ື㐠ື䛾つ๎ᛶ䜢ㄪ⠇䛩
䜛ᙺ๭䜢ᢸ䛳䛶䛔䜛䛣䛸䜢᫂䜙䛛䛻䛧䛯䚹䜎䛯䚸ᑠ⭠䛻䛚
䛡䜛䝁䝸䞁సືᛶ⚄⤒䛸⦪㉮ᖹ⁥➽⣽⬊㛫䛾⚄⤒➽ఏ
㐩䛻䛿䚸㻹䠎 䛸 㻹䠏 ୧䝃䝤䝍䜲䝥䛾่⃭䛜㔜せ䛷䛒䜚䚸᭦䛻
㻵㻯㻯 䛜㛵୚䛧䛶䛔䜛䛣䛸䜢᫂䜙䛛䛻䛧䛯䚹䜎䛯䚸ᑠ⭠ᖹ⁥
➽䛻Ⓨ⌧䛩䜛 㻭㼀㻼 ឤཷᛶ 㻷㻗 䝏䝱䝛䝹䠄㻷㻭㼀㻼 䝏䝱䝛䝹䠅䛾
⸆⌮Ꮫⓗᛶ㉁䜢᫂䜙䛛䛻䛩䜛୍⎔䛸䛧䛶䚸㔝⏕ᆺ䝬䜴䝇
䛾ᑠ⭠ᖹ⁥➽⣽⬊ᶆᮏ䛻䛚䛔䛶䚸ྛ✀ 㻷㻭㼀㻼 䝏䝱䝛䝹㛤
ཱྀ⸆䛻䜘䜚ㄏⓎ䛥䜜䜛 㻷㻭㼀㻼 䝏䝱䝛䝹㟁ὶ䜢グ㘓䛧䚸ྛ㛤
ཱྀ⸆䛾䠑䠌䠂᭷ຠ⃰ᗘ䠄㻱㻯㻡㻜 ್䠅䜢Ỵᐃ䛧䛯䚹㻌
䠄䠎䠅ႚ↮䛻䜘䜛Ẽ⟶ᨭᖹ⁥➽཰⦰ᶵ⬟䜈䛾ᙳ㡪㻌
Figure 1. Regulation of gut motility by cholinergic nerves
㻌 䝍䝞䝁↮䜢ᭀ㟢䛧䛯䝬䜴䝇䛛䜙స〇䛧䛯Ẽ⟶ᨭᖹ⁥➽䝸
䞁䜾ᶆᮏ䛻䛚䛔䛶䚸㧗⃰ᗘ 㻷㻗 ⁐ᾮ䜢㐺⏝䛧䛯᫬䛻⏕䛪
䠄䠎䠅ႚ↮䛻䜘䜛Ẽ⟶ᨭᖹ⁥➽཰⦰ᶵ⬟䜈䛾ᙳ㡪㻌
䜛཰⦰཯ᛂ䜢グ㘓䛧䚸㠀ႚ↮䝬䜴䝇䛾䜒䛾䛸ẚ㍑䞉ゎᯒ䛧
㻌 ୡ⏺ಖ೺ᶵ㛵䠄㼃㻴㻻䠅䛾ሗ࿌䛻䜘䜛䛸䚸඲ୡ⏺䛻䛚䛡
䛯䚹ႚ↮䝬䜴䝇䛾ᶆᮏ䛷䛿䚸㠀ႚ↮䝬䜴䝇䛸ྠᵝ䚸㧗⃰
䜛ႚ↮⪅䛾๭ྜ䛿⥲ேཱྀ䛾䠎䠎䠂䛻䜒ཬ䜃䚸ẖᖺ䚸⣙䠒䠌
ᗘ 㻷㻗 ⁐ᾮ䛻䜘䜚୍㐣ᛶ䛾཰⦰཯ᛂ䛜⏕䛨䛯䚹཰⦰཯ᛂ
䠌୓ே䜒䛾ே䛜䝍䝞䝁↮䛾ᭀ㟢䛻㛵㐃䛧䛯ཎᅉ䛻䜘䜚Ṛ
䛾኱䛝䛥䛻䛴䛔䛶䛿䚸୧⩌㛫䛻䛚䛔䛶ᕪ䛿ㄆ䜑䜙䜜䛺䛛
ஸ䛧䛶䛔䜛䚹ႚ↮䛿៏ᛶ㛢ሰ ᛶ⫵⑌ᝈ䠄㻯㻻㻼㻰䠅䛚䜘䜃
䛳䛯䛜䚸ႚ↮䝬䜴䝇䛷䛿䚸⸆≀䜢㐺⏝䛧䛶䛛䜙᭱኱཯ᛂ
ႍᜥ䛺䛹䛾䝸䝇䜽ᅉᏊ䛸䛧䛶ᗈ䛟▱䜙䜜䛶䛔䜛䚹䛣䜜䛿䚸ႚ
䛻⮳䜛䜎䛷䛾᫬㛫䛜᭷ព䛻ῶᑡ䛧䛶䛔䛯䚹䛣䜜䜙䛾⤖ᯝ
䛿䚸ႚ↮䛻䜘䜚Ẽ⟶ᨭᖹ⁥➽䛾⬺ศᴟ䛻ᑐ䛩䜛ឤཷᛶ
The World Health Organization (WHO) reported that
䛜ቑᙉ䛥䜜䜛䛣䛸䜢♧၀䛧䛶䛔䜛䚹㻌
22 % of the world's population aged over 15 are smokers,
㻌
and nearly 6 million people die from exposure to
㸱㸬Research projects and annual reports
cigarette smoke each year. It is well known that cigarette
It is well known that the motility of gastrointestinal
smoke is an important factor for chronic obstructive
tract is regulated by acetylcholine (ACh) released from
pulmonary disease (COPD) and asthma. It has been
cholinergic nerves,
act on the muscarinic
suggested that cigarette smoke exposure can cause
receptors. The receptors have been classified into five
airway hyperreactivity, which is involved in airway
subtypes including M1, M 2, M 3, M 4 and M 5. In
narrowing in patients with the diseases. However, little is
gastrointestinal
known
which
smooth
muscles,
two
subtypes
of
about
underlying
mechanisms
of
the
muscarinic receptor, M2 and M 3, are found with no
hyperreactivity induced by cigarette smoke. Therefore,
measurable quantities of other subtypes. As shown in
we are addressing the above issue using the mice which
Figure 1, stimulation of M2 and M 3 receptors by ACh
are exposed to cigarette smoke. Our studies may provide
2+
increases in the intracellular concentration of Ca ,
useful information to elucidate the pathophysiological
resulting in the smooth muscle contractions. Recently, it
conditions of COPD and asthma induced by cigarette
has been suggested that interstitial cells of Cajal (ICC),
smoking, leading to development of a novel effective
which exist in the myenteric and deep muscular plexus
medicine for the diseases. In this study, we collaborated
and express muscarinic receptors, are involved in the
with Laboratory of Immunopathology in Kyoto Sangyo
regulation of gut motility. However, roles of M2 and M 3
University.
receptors and ICC in regulating the gut motility by ACh
In this year, we recorded High K+-induced contractions
remain to be elucidated in detail. Therefore, we are
in bronchial muscle ring preparations from the mice
addressing the above issue using the M2 and/or M3
which were exposed to cigarette smoke (CS mice) and
muscarinic receptor knockout (KO) mice and ICC
compared data from the CS mice with data from the
deficient mice.
control mice which were exposed to the air instead of
(1) Mechanisms of gastrointestinal motility.
cigarette
We investigated roles of M2 and M 3 muscarinic receptor
smoke.
In
preparations
application of high K
+
from CS
mice,
solution induced a phasic
subtypes and ICC in the regulation of the peristalsis in
contraction as seen in control mice. Although the
small intestine. Our results show that M 2 receptors play
magnitude of the contractions was not obviously
an essential role in the generation of the peristalsis, and
different from that in preparations from control mice, the
that M 3 receptors have rather a modulatory role in
contractions reached a peak more quickly in CS
controlling periodicity of the peristaltic activity together
preparations than those in control preparations. These
with the ICC. We also investigated roles of M2 and M 3
results suggested that exposure to cigarette smoke can
muscarinic receptor subtypes and ICC in cholinergic
induce
hyperresponsiveness
to
depolarization
in
neuromuscular transmission in ileal longitudinal smooth
bronchial smooth muscles.
muscles. Our results suggested that both M 2 and M 3
㻌
receptors are involved in cholinergic neuromuscular
䠐䠊ㄽᩥ䠈ⴭ᭩䛺䛹㻌
transmission
H. Matsuyama, Y. Tanahashi, T. Kitazawa, M. Yamada, S.
together
with
ICC.
In
addition,
to
characterize pharmacological properties of ATP sensitive
Komori, T. Unno: Evidence for M 2 and M 3 muscarinic receptor
K+ (K ATP) channels expressed in the intestinal smooth
involvement in cholinergic excitatory junction potentials
muscles, we recorded the current through K ATP channels
through synergistic activation of cation channels in the
induced by several selective K ATP channel openers in
longitudinal muscle of mouse ileum. J. Pharmacol. Sci. 121(3),
small intestinal smooth muscle cells from wild type mice
and determined the 50 % effective concentration values
227-236
Y. Hirono, Y. Tanahashi, K. Sasaki, K. Konno, Y. Shirai, K.
(EC50) of the openers.
Kobayashi, A. Someya, S. Inaga, M. Sakura, K. E. Pinkerton,
(2) Effects of cigarette smoke exposure on contractility
M. Takeuchi: Alveolar macrophage functions and DNA damage
of bronchial smooth muscles
in cigarette smoke-exposed mice. Adv. Biosci. Biotechnol. 4,
alveolar macrophages by cigarette smoke. ➨42ᅇ᪥ᮏච␿Ꮫ
1-7
఍Ꮫ⾡㞟఍䠈༓ⴥᕷ䠈2013.12.11-13
Y. Tanahashi, N. Waki, T. Unno, H. Matsuyama, S. Iino, T.
Kitazawa, M. Yamada, S. Komori: Roles of M 2 and M3
䠒䠊䛭䛾௚≉グ஦㡯㻌
muscarinic receptors in the generation of rhythmic motor
䠍䠅㻌 እ㒊㈨㔠
activity in mouse small intestine. Neurogastroenterol. Motil. 25,
Ꮫ⾡◊✲ຓᡂᇶ㔠䞉ⱝᡭ◊✲䠄㻮䠅㻌
ㄢ㢟ྡ䠖䝮䝇䜹䝸䞁ཷᐜయ䛾⭠⟶㐠ືไᚚ䛻䛚䛡䜛 㻭㼀㻼 ឤཷ
e687–e697
ᛶ䠧䝏䝱䝛䝹䛾ᙺ๭䛸䛭䛾ศᏊᐇែ㻌
Y. Tanahashi, Y. Ichimura, K. Kimura, H. Matsuyama, S. Iino, S.
◊✲௦⾲⪅䠖Ჴᶫ㟹⾜㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻡㻙㻞㻣 ᖺ㻌 㻔㻟 ᖺ㻕㻌
Komori, T. Unno: Cholinergic neuromuscular transmission
mediated by interstitial cells of Cajal in the myenteric layer in
mouse
ileal
longitudinal
smooth
ி㒔⏘ᴗ኱Ꮫ㻌 ≉ᐃㄢ㢟◊✲㻌
ㄢ㢟ྡ䠖ႚ↮䛻䜘䜛Ẽ⟶ᨭᖹ⁥➽䛾཰⦰㐣ᩄᛶ䛻ᑐ䛩䜛⸆
muscles.
Naunyn-Schmiedeberg's Arch. Pharmacol. in press DOI
⌮䞉ච␿Ꮫⓗ◊✲㻌
10.1007/s00210-013-0944-2
◊✲௦⾲⪅䠖Ჴᶫ㟹⾜㻘㻌 ྲྀᚓᖺᗘ䠖㻴㻞㻠㻙㻞㻡 ᖺ㻌 㻔㻞 ᖺ㻕㻌
Ჴᶫ㟹⾜䚸ᾏ㔝ᖺᘯ䚸ᯇᒣຬே䚸໭⃝ከ႐㞝䚸ᑠ᳃ᡂ୍: 䝬䜴
䝇ᑠ⭠ᖹ⁥➽䛾䝮䝇䜹䝸䞁సືᛶ ཰⦰ㄪ⠇ᶵᵓ䛻䛚䛡䜛ATP
䠎䠅㻌 䛭䛾௚㻌 㻌
ᢸᙜㅮ⩏䠖ື≀་⛉Ꮫᴫㄽ䚸໬Ꮫ㏻ㄽ 㻭䚸໬Ꮫ㏻ㄽ 㻮䚸ᇶ♏
+
ឤ ཷ ᛶ K 䝏䝱䝛䝹䛾ᙺ ๭ 䛸䛭䛾᝟ ሗ ఏ㐩 ᶵ ᵓ. ᪥ ᮏ⑓ ែ ⏕
໬Ꮫ䊠䚸ᇶ♏໬Ꮫ䊡䚸⸆⌮Ꮫ䞉ẘᛶᏛ䚸ᐇ㦂ື≀Ꮫ䞉ẘᛶ
⌮Ꮫ㞧ㄅ䚸22䠄䠄 3䠅䚸36-38
Ꮫᐇ⩦䚸ᇶ♏≉ู◊✲㻌
Ჴᶫ㟹⾜䚸➉ෆᐇ: 䝬䜴䝇Ẽ⟶ᖹ⁥➽ᶆᮏ䛻䛚䛡䜛ᙇຊ ᐃἲ
㻌
䛾㛤Ⓨ. ி㒔⏘ᴗ኱Ꮫ⥲ྜᏛ⾡◊✲ᡤᡤሗ䚸8䚸131-136
ᒸ⏣኱ᆅ䚸ᘅ㔝⏤㔛Ꮚ䚸⏣୰⨾Ꮚ䚸బ䚻ᮌ୍㤿䚸Ჴᶫ㟹⾜䚸㧗
ᶫ⣧୍䚸బ಴ṇ᫂䚸➉ෆᐇ䠖㻌 ᪥ᮏᅜ⏘䝝䝏䝭䝒䛻䜘䜛⫵⬊䝬䜽
䝻䝣䜯䞊䝆䛾ච␿ᶵ ⬟䛻ཬ䜌䛩ᙳ 㡪 㻚 ி㒔 ⏘ᴗ኱ Ꮫඛ➃ ⛉
Ꮫᢏ⾡ᡤᡤሗ䚸㻝㻞䚸㻟㻟㻙㻠㻠㻌
㻌
䠑䠊Ꮫ఍Ⓨ⾲䛺䛹㻌
Y. Tanahashi, T Unno, H. Matsuyama, T. Kitazawa, M. Yamada, J.
Wess, S. Komori䠖 Muscarinic regulation of ATP sensitive K+
channels in mouse ileal smooth muscles. ➨86ᅇ᪥ᮏ⸆⌮Ꮫ
఍ᖺ఍䠈⚟ᒸᕷ䠈2013.3.21-23
T. Unno, T. Katsurada, H. Matsuyama, Y. Tanahashi, T. Kitazawa,
M. Yamada, J. Wess, S. Komori: Involvement of M 2 or M 3
muscarinic receptor-coupled signalling molecules in the
activation of muscarinic cation channels in mouse ileal smooth
muscle cells. ➨ 86 ᅇ ᪥ ᮏ ⸆ ⌮ Ꮫ ఍ ᖺ ఍ 䠈 ⚟ ᒸ ᕷ 䠈
2013.3.21-23
Ჴᶫ㟹⾜䚸ᾏ㔝ᖺᘯ䚸ᯇᒣຬே䚸໭⃝ከ႐㞝䚸ᑠ᳃ᡂ୍䠖䝬䜴䝇
ᑠ⭠ᖹ⁥➽䛾䝮䝇䜹䝸䞁సືᛶ཰⦰ㄪ⠇ᶵᵓ䛻䛚䛡䜛ATPឤ
ཷᛶ K+ 䝏䝱䝛䝹䛾ᙺ๭䛸䛭䛾᝟ሗఏ㐩ᶵᵓ 䚸➨䠎䠏ᅇ᪥ᮏ⑓
ែ ⏕ ⌮ Ꮫ఍ 䝃䝔䝷䜲䝖䝉䝭䝘䞊䠃䝕䜱䝇䜹䝑䝅䝵䞁䠈ᮾ ி 䠈
2013.8.2-4䠄ᣍᚅㅮ₇䠅
K. Sasaki, Y. Hirono, Y. Tanahashi, M. Sakura, T. Ishida, M.
Takeuchi: Effect of cigarette smoking on infiltration of
neutrophils in LPS-induced lung inflammation. ➨42ᅇ᪥ᮏච
␿Ꮫ఍Ꮫ⾡㞟఍䠈༓ⴥᕷ䠈2013.12.11-13
Y. Hirono, K. Sasaki, Y. Tanahashi, M. Sakura, T. Ishida, S. Inaga,
M. Takeuchi: The mechanism of inhibition of apoptosis in
⸆⌮Ꮫ◊✲ᐊ䝯䞁䝞䞊㻌
ಎᢎ᝼㩷 ⷏㊁㩷 ૫એ
∛ේᓸ↢‛ቇ⎇ⓥቶ㩷
Laboratory of Virology㩷
Associate Prof. Yoshii Nishino, DVM,
Ph.D
䋱䋮⎇ⓥ᭎ⷐ㩷
㩷 ⑳㆐䈲ᄙ䈒䈱ᓸ↢‛䈮࿐䉁䉏䈩↢䈐䈩䈇䉎䇯䉡䉟䊦䉴
㪋䋩䊗䊦䊅∛⊒∝䈮㑐ਈ䈜䉎ኋਥ࿃ሶ䈫ⅣႺ࿃ሶ䈮䈧䈇
䈲ᓸ↢‛䈱৻ຬ䈪䈅䉎䈏䇮⥄Ꮖⶄ⵾䈱䈢䉄䈮ᔅⷐ䈭ᦨ
ዊ㒢ᐲ䈱ㆮવሶ䈚䈎ᜬ䈢䈭䈇䈢䉄䇮േ‛䉇ᬀ‛䈮ነ↢
䈩㩷
㪌䋩䉡䉟䊦䉴Ⱞ⊕⾰䈱⚦⢩ౝዪ࿷ᯏ᭴䈫∛ේᕈ䈫䈱㑐ㅪ
䈚䇮ኋਥ⚦⢩ౝ䈱ዊེቭ䉕᜙୫䈚䈩Ⴧᱺ䈜䉎䇯䈠䈱⚿ᨐ䇮
ᕈ䈮䈧䈇䈩㩷
ነ↢䈚䈢⚦⢩䈱⎕უ䇮⚦⢩ᯏ⢻䈱㓚ኂ䈫䈇䈦䈢⋥ធ⊛
㪍䋩ኅ⇓䊶䊕䉾䊃䈮䈍䈔䉎䊗䊦䊅∛䉡䉟䊦䉴ᗵᨴ∉ቇ⺞ᩏ㩷
䈭㓚ኂ䇮䈅䉎䈇䈲䉡䉟䊦䉴᛫ේ䉕⊒⃻䈚䈢ᗵᨴ⚦⢩䈏ኋ
㪎䋩᛫䉡䉟䊦䉴ᵴᕈ‛⾰䈱⸃ᨆ㩷
ਥ఺∉ᔕ╵䈎䉌䇸⇣‛䇹䈫⹺⼂䈘䉏䈩ឃ㒰䈘䉏䉰䉟䊃䉦䉟
㩷
䊮╬䈱ᶧᕈ࿃ሶ䈱↥↢䈏⺃ ዉ䈘䉏䉎䈫䈇䈦䈢㑆ធ⊛䈭
䋲䋮ᧄᐕᐲ䈱⎇ⓥᚑᨐ㩷
㓚ኂ䉕ᒁ䈐⿠䈖䈜䇯䈖䈱䉋䈉䈭ᗵᨴ୘૕䈮䈍䈔䉎᭽䇱䈭
㩷 䇸᧲੩ㄭ㇠䈱䉟䉣䊈䉮䈮䈍䈔䉎䊗䊦䊅∛䉡䉟䊦䉴ᗵᨴ∉
ᓇ㗀䇮䈇䉒䉉䉎∛᳇䉕⿠䈖䈜䈱䈪䈅䉎䇯⑳㆐䈱⎇ⓥቶ䈪
ቇ⺞ᩏ䇹
䈲䇮േ‛䈅䉎䈇䈲ੱ₞౒ㅢ䈱䉡䉟䊦䉴ᗵᨴ∝䇮․䈮␹⚻
䊗䊦䊅∛ 䉡䉟䊦䉴䋨BDV䋩䈲䊈䉮䈮ᗵ ᨴ 䈜䉎䈫␹ ⚻ ∝
䉡䉟䊦䉴∝䈮⥝๧䈏䈅䉎䇯䈭䈟䈭䉌䇮ਛᨔ␹⚻♽䉕ᅢ䉃
⁁䉕ᒁ䈐⿠䈖䈜䇯⑳㆐䈲䇮᧲੩ㄭ㇠࿾ၞ䈱ⶄᢙ䈱േ‛
䉡䉟䊦䉴䈲఺∉ᔕ╵䉕⺃ዉ 䈚䈮䈒䈒䇮䉁䈢ⴊᶧ⣖㑐㐷䈱
∛㒮䈮᧪㒮䈚䈢 199 ඘䈱䉟䉣䊈䉮䈮䈍䈇䈩 BDV ᗵᨴ⺞
ሽ࿷䈮䉋䉍ઁ䈱⤳ེ䈮Ყ䈼ലᨐ⊛䈭ൻቇ≮ᴺ೷䈏㒢䉌
ᩏ䉕ⴕ䈦䈢䇯
䉏䉎䈖䈫䈎䉌ᴦ≮ᴺ䈏࿎㔍䈭႐ว䈏ᄙ䈒䇮␠ળ⊛䈮䈠䈱
GST-BDVp24 䈅䉎䈇䈲㵥p40 ᛫ේ䈮ኻ䈜䉎ⴊẏ᛫૕䈏
⸃᳿䈏ᦸ䉁䉏䈩䈇䉎䈎䉌䈪䈅䉎䇯㩷
䉡䉣䉴䉺䊮䊑䊨䉾䊃ᴺ䈮䉋䉍ᬌ಴䈘䉏䈢႐ว䉕᛫૕㓁ᕈ䈫
㩷 ⑳㆐䈲䇮䇸䉡䉟䊦䉴ᕈ␹⚻䊶♖␹␹⚻∔ᖚ䇹䉕⎇ⓥ䈜䉎
⸻ᢿ䈚䇮BDV 䈮ᗵᨴ䈚䈢䋨ጁᱧ䈏䈅䉎䋩䈫್ቯ䈚䈢䇯
䈢䉄䈮䇮䊗䊦䊅∛䉡䉟䊦䉴䋨BDV䋩ᗵᨴ䈮䉋䉍ᒁ䈐⿠䈖䈘䉏
䉎䊗䊦䊅∛䈮ὶὐ䉕⛉䉍⎇ⓥ䉕ⴕ䈦䈩䈐䈢䇯䊗䊦䊅∛䈲
䉡䊙䉇䊍䉿䉳䈮ᜬ⛯⊛䈮ᗵᨴ䈚䇮ᤨ䈮⥌ᱫ⊛䈭␹⚻∔ᖚ
䉕ᒁ䈐⿠䈖䈜∛᳇䈫䈚䈩 100 ᐕએ਄೨䈎䉌⍮䉌䉏䈩䈇䈢䇯
ᦨㄭ䈪䈲䇮䊈䉮䇮䉟䊇䇮䉝䊤䉟䉫䊙䇮㠽㘃䇮䊆䊖䊮䉱䊦䇮䈘䉌
䈮䊍䊃䉕฽ 䉃᏷ᐢ 䈇᷷ ⴊ േ ‛ 䈮ᗵ ᨴ 䈏⹺ 䉄䉌䉏䉎ᣂ⥝
ᗵᨴ∝䈫䈚䈩⹺⼂䈘䉏䈩䈇䉎䇯䈚䈎䈚䈭䈏䉌䇮䈇䉁䈣∛᳇
䈱⊒∝䊜䉦䊆䉵䊛䈲లಽ䈮⸃᣿䈘䉏䈩䈇䈭䈇䇯䉁䈢䇮䊍䊃
䉕฽䉃䈾䈫䉖䈬䈱േ‛䈮䈍䈇䈩ਥ䈢䉎વ᠞⚻〝䈲᣿䉌䈎
䈪䈲䈭䈇䇯․䈮䊍䊃䈪䈲∛ේᕈ䈜䉌᣿䉌䈎䈮䈘䉏䈩䈇䈭䈇䇯
⑳㆐䈲䇮BDV 䈱ᜬ⛯ᗵᨴᕈ䈫∛ේᕈ䉕ᄙⷺ⊛䈮⸃ᨆ䈜
䉎⋡⊛䈪䇮䊤䉾䊃䉇䊙䉡䉴╬䈱ᗵᨴ䊝䊂䊦േ‛䈮䈍䈔䉎
∛ᘒ䋨ㆇേ㓚ኂ䈫ⴕേቇ⊛⇣Ᏹ䋩䈱⸃ᨆ䈫䇮㊁ᄖ䈱േ‛
䈮䈍䈔䉎ᗵᨴ∉ቇ⺞ᩏ䉕ਛᔃ䈮એਅ䈱䉋䈉䈭ὐ䈮䈧䈇
䈩⎇ⓥ䉕ⴕ䈦䈩䈇䉎䇯
1䋩䉡䉟䊦䉴䉭䊉䊛䈮䈍䈔䉎∛ේᕈ㑐ㅪㆮવሶ䈱หቯ䈫䇮
䊤䉾䊃䈍䉋䈶䊙䉡䉴䈮䈍䈔䉎∛ᘒ䈱䉡䉟䊦䉴ቇ⊛䇮∛ℂ
ቇ⊛䇮ⴕേቇ⊛⸃ᨆ
2䋩⣖䊶␹⚻♽⚦⢩䈮䈍䈔䉎 TGF-β 㑐ㅪㆮવሶ䈱⊒⃻䈫
䉡䉟䊦䉴∛ේᕈ䈫䈱㑐ㅪᕈ䈮䈧䈇䈩
3䋩䉡䉟䊦䉴䈏ኋਥേ‛䈮㚔ൻ䈜䉎㓙䈱䉡䉟䊦䉴䉭䊉䊛䈱
ᄌ⇣ᯏ᭴䈮䈧䈇䈩
䈠䈱⚿ᨐ䇮53 ඘䋨27.1䋦䋩䈱䉟䉣䊈䉮䈮䈍䈇䈩䇮BDV
㥲⮮ᢅਯ䇮⷏㊁૫એ䋮䉴䊃䊧䉴ᕈ⣖ᯏ⢻㓚ኂ䈮䈍䈔䉎䉡䉟䊦䉴
․⇣᛫૕䈏ᬌ಴䈘䉏䈢䇯⥝๧ᷓ䈇䈖䈫䈮䇮᛫૕㓁ᕈ䈫⸻
ᜬ⛯ᗵᨴ䈱ᓇ㗀䋮੩
੩ ㇺ↥ᬺᄢቇ✚วቇⴚ⎇ⓥᚲᚲႎ䋮
ᢿ䈘䉏䈢䉟䉣䊈䉮䈱ഀว䈲䇮ஜᐽ⟲䋨29.8䋦䋩䇮␹⚻∝⁁
12:93-99. 2013
䉕઻䉒䈭䈇∔ᖚ⟲(22.2䋦)䇮␹⚻∔ᖚ⟲䋨33.3䋦䋩䈱 3 ⟲
㑆䈪᦭ᗧᏅ䈏䈭䈎䈦䈢䇯䉁䈢䇮BDV ․⇣᛫૕䈲 1 ᱦᧂ
㩷
ḩ䈱䉟䉣䊈䉮䈮䈍䈇䈩䉅⹺䉄䉌䉏䈢䇯᛫૕㓁ᕈ₸䈲䇮ᕈ
䋵䋮ቇળ⊒⴫䈭䈬㩷
೎䇮ᐕ㦂⟲䇮䈠䈚䈩ណ᧚䈚䈢ቄ▵㑆䈪᦭ᗧᏅ䈲⹺䉄䉌䉏
㥲⮮㩷 ᢅਯ䇮ᏒᎹ㩷 䉂䈭䉂䇮ዊ㊁㩷 㓉␭䇮⷏㊁㩷 ૫એ䋺⣖䈮䈍䈔䉎
䈭䈎䈦䈢䇯
Timmᨴ⦡ᴺ䈱ౣᬌ⸛䇯╙156࿁ᣣᧄ₞කቇળ㩷 2013.9.20䋨ጘ
㒂Ꮢ䋩
એ਄䈱⚿ᨐ䈎䉌䇮BDV 䈏⥄ὼᗵᨴ䈚䈢䊈䉮䈏䊗䊦䊅
∛䉕⊒∝䈜䉎䈮䈲䇮䈘䉌䈮૗䉌䈎䈱ⷐ࿃䈏ᔅⷐ䈪䈅䉐䈉䈖
㩷
䈫䇮䈠䈚䈩 BDV 䈲䊈䉮䈮䈍䈇䈩ု⋥વ᠞䈚䈩䈇䉎น⢻ᕈ
䋶䋮䈠䈱ઁ․⸥੐㗄㩷
䈏␜ໂ䈘䉏䈢䇯
䋱䋩㩷 ᄖㇱ⾗㊄
㩷
⑼ቇ⎇ⓥ⾌⵬ഥ㊄䊶ၮ⋚⎇ⓥ䋨C䋩
⺖㗴ฬ䋺䉡䉟䊦䉴ᕈ␹⚻∔ᖚ䈮ᓇ㗀䉕෸䈿䈜ኋਥⷐ࿃䈫Ⅳ
㧟㧚Research projects and annual reports
Borna
disease
virus
(BDV)
infection
Ⴚⷐ࿃
causes
⎇ⓥઍ⴫⠪䋺⷏㊁૫એ㪃㩷 ขᓧᐕᐲ䋺㪟㪉㪌㪄㪉㪎 ᐕ㩷 㩿㪊 ᐕ㪀㩷
neurological disease in cats. Here we report BDV
infection on 199 hospitalized domestic cats in Tokyo
੩ㇺ↥ᬺᄢቇ㩷 䇸․ቯ⺖㗴⎇ⓥ䇹㩷 㩷
area. BDV infection was evaluated by detection of
⺖㗴ฬ㩷 䋺䉴䊃䊧䉴ᕈ⣖ᯏ⢻㓚ኂ䈮䈍䈔䉎䉡䉟䊦䉴ᜬ⛯ᗵᨴ䈱
plasma antibody against BDV-p24 or -p40. BDV-specific
ᓇ㗀㩷 㩷
antibodies
⎇ⓥಽᜂ⠪㧦⷏㊁૫એ㧔⎇ⓥઍ⴫⠪䋺㩷 㥲⮮ᢅਯ䋩䇮ขᓧᐕ
were
detected
in
54
cats
(27.1%).
ᐲ㧦* ᐕ
㧞ᐕ
Interestingly, the percentage of seropositive cats was not
significantly different among three clinical groups, i.e.,
䋲䋩㩷 ⍮⽷ᮭ╬㩷 㩷
healthy (29.8%), neurologically asymptomatic disease
‫․ޣ‬㗿⇟ภ䇽㩷 ․㗿 㪉㪇㪈㪊㪄㪈㪈㪇㪏㪋㪐㩷
䇼ฬ⒓䇽㩷 䉡䉟䊦䉴ਇᵴൻ೷䇮᛫⩶೷䇮䉡䉟䊦䉴ਇᵴൻᣇᴺ䇮ਗ
(22.2%) and neurological disease (33.3%). The specific
䈶䈮䇮᛫⩶ᣇᴺ㩷
antibodies were present even in cats aged below one year.
䇼಴㗿ੱ䇽㩷 ቇᩞᴺੱ੩ㇺ↥ᬺᄢቇ䇮ᩣᑼળ␠䉴䉳䊢䊮䊶䉳䊞
The seropositive ratio was constant, irrespective of age
䊌䊮㩷
and sampling season. The present study suggests that
additional factors are required for onset of Borna disease
䋳䋩㩷 ቇᄖᵴേ㩷 㩷
on naturally infected cats, and that BDV is transmitted
ᣣᧄ䊗䊦䊅䉡䉟䊦䉴⎇ⓥળ㪑䋺೽ળ㐳㩷
through vertical routes in cats.
⑼ቇ⎇ⓥ⾌ᆔຬળኾ㐷ᆔຬ㩷
䋴䋩㩷 ฃ⾨╬㩷 㩷
㩷
䈭䈚㩷
䋴䋮⺰ᢥ䋬⪺ᦠ䈭䈬㩷
Murakami, M., Shirai, M., Ooishi, R., Tsuburaya, A., Asai, K.,
Hashimoto, O., Ogawa, K., Nishino, Y., and Funaba, M.
㩷
䋵䋩㩷 䈠䈱ઁ㩷 㩷
੩ㇺ↥ᬺᄢቇ䊶੩ㇺᏒቇⴚ੤ᵹ੐ᬺ䈮䈍䈔䉎౒ห⎇ⓥ䇮㩷
Expression of activin receptor-like kinase 7 in adipose tissues.
Biochemical Genetics, 51: 202-210. 2013.
⷏㊁૫એ䋺䊗䊦䊅∛䉡䉟䊦䉴ᗵᨴ∝䇮ᗵᨴ∝∝୥⟲䋨╙䋲 䋩਄㩷
㩷 㩷 䈭䉌䈶䈮ⴡ↢ⅣႺ⎇ⓥᚲ㘩⡺ᬌᩏㇱ㐷䈫䈱วหળ⼏㩷
㩷 㩷 䋨⸘ 㪌 ࿁䋩㩷
↢ ℂቇ ㆙㓒ᮨ ᡆ⻠ ⟵䋨㠽ข ᄢቇ䇮ᵻ ㊁ᷕ ಎ ᢎ᝼䈮䉋䉎䇸ⴊ
∛ේ૕೎ᗵᨴ∝✬.㩷 IV.䉡䉟䊦䉴ᗵᨴ∝㩷 RNA䉡䉟䊦䉴ᗵᨴ∝.㩷
♧⺞▵䈫♧ዩ∛䇹䇮㪉㪇㪈㪊㪅㪎㪅㪈䋩䈱䉮䊷䊂䉞䊈䊷䊃㩷
೎ ౠᣣᧄ⥃ᐥ㩷 pp.506-509 ᣂ㗔ၞ೎∝୥⟲䉲䊥䊷䉵㩷 No.24.㩷
䉥䊷䊒䊮䉨䊞䊮䊌䉴䈮䈍䈔䉎ᮨᡆታ㛎䋨㪉㪇㪈㪊㪅㪏㪅㪈㪎䋩㩷
੩ㇺᏒ┙⚡㊁㜞╬ቇᩞߣߩ㜞ᄢㅪ៤᝼ᬺ
↢‛‫ޟ‬ㆮવሶ⸻
ᢿᴺߩታ㓙‫ޠ‬㧔㧕
2013.䋨✚⺑䋩
ᨴ⼱ᪧ䇮ᳰ᳗లብ䇮ᄢ⷏ୃ䇮Velado Fernandez, Igor䇮⷏㊁૫
એ䇮೨↰⑺ᒾ䋮੩ㇺᏒጊ⑼඙䈪㚟㒰䈘䉏䈢䉟䊉䉲䉲䈮ነ↢䈚
੩ ㇺ↥ᬺᄢቇ✚วቇⴚ⎇ⓥᚲᚲႎ䋮
䈩䈇䈢䊙䉻䊆㘃䈱⸃ᨆ䋮੩
㩷
8:57-62. 2013.
㩷
㩷
㩷
㩷
⑺䈱䈍⺀↢ળ䇯㪊䋬㪋 ࿁↢䈏ឥ䈇⾟䉇䈎䈮䋣㩷
㩷
㩷
㩷
㪋 ࿁↢䈫࿑ᦠ㙚ⵣ䈪⸥ᔨ᠟ᓇ䇯䈤䉊䈦䈫䉝䊷䊃䋿㩷
㩷
㩷
㩷
ᢎ᝼㩷 ೨↰㩷 ⑺ᒾ
ⅣႺⴡ↢ቇ⎇ⓥቶ
Prof. Akihiko Maeda, D.V.M.. Ph D㩷
㪣㪸㪹㫆㫉㪸㫋㫆㫉㫐㩷㫆㪽㩷㪜㫅㫍㫀㫉㫆㫅㫄㪼㫅㫋㪸㫃㩷㪟㫐㪾㫀㪼㫅㪼㩷
㩷
.
䋱䋮⎇ⓥ᭎ⷐ㩷
⑳䈢䈤䈱๟࿐䈮䈲䇮ᢙ䈋ಾ䉏䈭䈇⒟䇮᭽䇱䈭ᓸ↢ ‛
䈏ሽ࿷䈜䉎䇯䈠䈱ਛ䈮䈲䇮േᬀ‛䉇䊍䊃䈮ᗵᨴ䈚䈩∛᳇
䉕ᒁ䈐⿠䈖䈜䉅䈱䉅䈅䉏䈳䇮䈠䈉䈪䈭䈇䉅䈱䉅䈅䉎䇯䉁䈢䇮
⣺ౝ⚦⩶䈱䉋䈉䈮േ‛䈱⣺ౝ䈪㘩‛䈱ᶖൻ䉕ഥ䈔䉎䉅
䈱䉇䇮േᬀ‛䈱ㅴൻ䈱ㆊ⒟䈪㊀ⷐ䈭ᓎഀ䉕ᜂ䈦䈩䈇䉎䈫
⠨䈋䉌䉏䈩䈇䉎䉅䈱䉁䈪䇮᭽䇱䈭䉅䈱䈏ሽ࿷䈜䉎䇯䈖䈱᭽
䈮䇮⑳䈢䈤䈱๟䉍䈮ሽ࿷䈜䉎ᓸ↢‛䈲䇮᭽䇱䈮േ‛䉇ᬀ
‛䈫⋧੕䈮ᓇ㗀䈚ว䈇䇮↢ᘒቇ⊛䈭䊚䉪䊨䉮䉴䊝䉴䈫䊙䉪
䊨䉮䉴䊝䉴䉕ᒻᚑ䈚䈩䈇䉎䇯㩷
ᧄ⎇ⓥಽ㊁䈪䈲䇮ᓸ↢‛䈱ਛ䈪䉅․䈮䇸േ‛䈎䉌䊍䊃䇹
䈮ᗵᨴ䈜䉎ੱ₞౒ㅢᗵᨴ∝䋨㪱㫆㫆㫅㫆㫊㫀㫊䋩䉕ᒁ䈐⿠䈖䈜∛
ේᓸ↢‛䈮䈧䈇䈩䇮∛ේᕈ⊒⃻䊜䉦䊆䉵䊛䉇ⅣႺਛ䈪
䈱ሽ࿷᭽ᑼ䉕⸃᣿䈜䉎䈢䉄䈱ၮ␆⊛䈭⎇ⓥ䉕ⴕ䈦䈩䈇
䉎䇯ౕ૕⊛䈭⎇ⓥኻ⽎䈲䇮Ⰶ䉇䉻䊆╬䈱▵⿷േ‛䈏ᇦ
੺䈜䉎ੱ₞౒ㅢᗵᨴ∝䈪䈅䉎㩿࿑ 㪈㪀䇯ㄭᐕ䈱࿾⃿᷷ᥦൻ
䈮઻䈉ᇦ੺Ⰶ䈱↢ᕷၞ䈱᜛ᄢ䈫䇮䈠䉏䈮઻䈉ᒰ⹥ᗵᨴ∝
䈱ᵹⴕၞ䈱᜛ᄢ䈏ෂᗋ䈘䉏䈩ਭ䈚䈇䇯ᣣᧄ䈮䈍䈇䈩䉅䇮
ᶏᄖ䈪ᵹⴕ䈚䈩䈇䉎䉡䉟䊦䉴䉇⚦⩶╬䈱∛ේ૕䈱ଚ౉䈫䇮
࿖ౝ䈪䈱ᵹⴕ䈻䈱ኻ╷䈏ᕆോ䈫䈭䈦䈩䈇䉎䇯䈠䈖䈪ᧄ⎇
ⓥቶ䈪䈲䇮ਥ䈮એਅ䈱⎇ⓥ䊁䊷䊙䈮䈧䈇䈩⎇ⓥ䈚䈩䈇
䉎䇯㩷
(1) Ⰶ䈍䉋䈶䉻䊆ᇦ੺ ᕈ ੱ₞ ౒ ㅢᗵ ᨴ ∝䈱੩ ㇺᏒ 䈮
䈍䈔䉎ᗵᨴ∉ቇ⊛⸃ᨆ䈫䇮ᣂⷙᬌᩏᴺ䉇䊪䉪䉼䊮䉕
㐿⊒䈜䉎䇯㩷
(2) Ⰶ䈍䉋䈶䉻䊆ᇦ੺ᕈੱ₞౒ㅢᗵᨴ∝䉕ᒁ䈐⿠䈖䈜
∛ේᓸ↢‛䈱ಽሶ↢‛ቇ⊛⸃ᨆ䉕ⴕ䈉䇯㩷
㩷
䈍䉋䈶┙๮㙚ᄢቇ䈱ਛ⼱㩷 ಎᢎ᝼䈫หᄢᄢቇ㒮 㪊 ᐕ↢
䈱☨ፉ 䈘䉖䇮㤗↢ᄢቇ 䈱ੑ ↉㩷 ቴຬ ⎇ⓥ ຬ䈫䈱౒ห ⎇
ⓥ䈫䈚䈩ⴕ䈦䈢䇯Ⰶ䉇䉻䊆╬䈱ๆⴊᕈ▵⿷േ‛䈲䇮᭽䇱
䈭ᗵᨴ∝䉕േ‛䈎䉌ੱ䈮ᇦ੺䈜䉎䇯ᇦ੺䈘䉏䉎વᨴ∛䈲
Ⰶ䉇䉻䊆䈱⒳㘃䈮䉋䉍⇣䈭䉎䇯䈚䈢䈏䈦䈩䇮ੱ䈏ዬ૑䈜䉎
ⅣႺਛ䈮↢ᕷ䈜䉎Ⰶ䉇䉻䊆䈱⒳㘃䈮䉋䈦䈩䇮ᒰ⹥࿾ၞ
䈪ᵹⴕ䈜䉎ᗵᨴ∝䈏⇣䈭䉎䉅䈱䈫⠨䈋䉌䉏䉎䇯䈠䈖䈪䇮ᧄ
ᐕᐲ䈪䈲䇮䉁䈝䇮੩ㇺᏒౝ䈪Ⰶ䉇䉻䊆䉕ណข䈚䇮⒳䉕ฎ
ౖ⊛䈭ᒻᘒ㗵 ⊛㐓೎ᴺ䈮ᓥ 䈦䈩หቯ䈚䈢䇯䉁䈢䇮ᒻ ᘒ
ቇ⊛䈮㐓೎䈏࿎㔍䈪䈅䉎䉝䉦䉟䉣䉦䈫䉼䉦䉟䉣䉦䈮䈧䈇
䈩䈲䇮㪧㪚㪩 ᴺ䉕↪䈇䈩㐓೎䈚䈢䇯䈘䉌䈮䇮Ⰶ䉇䉻䊆䈏଻᦭
䈜䉎∛ ේ ᓸ ↢ ‛ 䋨ฦ ⒳ 䈱䊐 䊤 䊎 䉡䉟 䊦䉴䉇䊥䉬䉾䉼 䉝 䇮
㪪㪟㪝㪪㪭䇮㠽䊙䊤䊥䉝䇮䉟䊇䊐䉞䊤䊥䉝╬䋩䉕䇮∛ේ૕䉕․⇣
⊛䈮ᬌ಴䈜䉎 㪧㪚㪩 䈅䉎䈇䈲 㪩㪫㪄㪧㪚㪩 ᴺ䉕↪䈇䈩䇮䈠䈱
ᬌ಴䉕⹜䉂䈢䈫䈖䉐䇮䊐䊤䊎䉡䉟䊦䉴䈱৻⒳䈍䉋䈶䊥䉬䉾䉼
䉝䈏ᬌ಴䈘䉏䈢䇯䉁䈢䇮∛ේ૕ಽ㔌䉕⹜䉂䈢䈫䈖䉐䇮䈖䉏
䉁䈪䈮ᣣᧄ䈪ႎ๔䈱䈭䈇䉡䉟䊦䉴⒳䈏ಽ㔌䈘䉏䈢䇯㩷
㩷
㩿㪉㪀 Ⰶ ᇦ ੺ ᕈ ੱ ₞ ౒ ㅢ ᗵ ᨴ ∝ 䈪䈅䉎䊐䊤䊎䉡䉟䊦䉴䈱
ಽሶ↢‛ቇ⊛⸃ᨆ㩷
㩷 䊐䊤䊎䉡䉟䊦䉴ᗵᨴ䈲䇮䉡䉟䊦䉴☸ሶ䈱⴫㕙䈮ሽ࿷䈜䉎
⤑Ⱞ⊕⾰䈱৻⒳䈪䈅䉎 㪜 Ⱞ⊕⾰䈫䇮⚦⢩⴫㕙Ⱞ⊕⾰
䋨੹䈣⛔৻䈚䈢⷗⸃䈲䈭䈇䋩䈫䈱⚿ว䈮䉋䉍ᆎ䉁䉎䈫䈘䉏䈩
䈇䉎䇯䈚䈎䈚䇮䈠䈱⹦⚦䈭䊜䉦䊆䉵䊛䈲ਇ᣿䈭ὐ䈏ᄙ䈇䇯
⊕⾰䈫⋧੕૞↪䈜䉎ኋਥ䉺䊮䊌䉪⾰䈱ᬌ⚝䊶หቯ䉕ⴕ䈇䇮
㩷
ᐞ䈧䈎䈱୥⵬ Ⱞ⊕⾰䈫䈭䉎ኋਥⰮ⊕⾰䉕หቯ䈚䈢䇯⃻
㩷
㩷
㩷 ੩ㇺᏒⅣႺⴡ↢⎇ⓥᚲ䈱ᳰ᳗䇮ㄭ㊁䇮᧖ᳯ㩷 ⎇ⓥຬ
䈠䈖䈪ᧄ⎇ⓥቶ䈱ᄢቇ㒮↢䈱䉟䉯䊷䊦ำ䈫䈫䉅䈮䇮㪜 Ⱞ
㩷
㩷
䋲䋮ᧄᐕᐲ䈱⎇ⓥᚑᨐ㩷
㩿㪈㪀 Ⰶ 䈍䉋䈶䉻䊆ᇦ ੺ ᕈੱ ₞ ౒ㅢ ᗵ ᨴ∝ 䈱੩ㇺ Ꮢ 䈮
䈍䈔䉎ᗵᨴ∉ቇ⊛⸃ᨆ㩷
࿷䇮ਔⰮ⊕⾰䈱⋧੕૞↪䉕⏕⹺䈜䉎䈫䈫䉅䈮䇮䉡䉟䊦䉴
ᐯ໱မ
㩷
ᗵᨴ䈮䈍䈔䉎ᒰ⹥Ⱞ⊕⾰䈱ᓎഀ䈮䈧䈇䈩ᬌ⸛䈚䈩䈇䉎䇯
䉁䈢䇮䊐䊤䊎䉡䉟䊦䉴⎇ⓥ䈱䈢䉄䈱㆏ౕ䈫䈚䈩䇮䊧䊘䊷䉺䊷
Ⱞ⊕⾰ㆮવሶ䉕䉭䊉䊛ㆮવሶ䈫䈚䈩฽䉃䊐䊤䊎䉡䉟䊦䉴
㩷
᭽☸ሶ䈱◲ଢ䈪቟ో䈭૞⵾ᴺ䉕㐿⊒䈚䈢䇯㩷
㩷
㩷
࿑ 㪈㪅㩷 ▵⿷േ‛ᇦ੺ᕈੱ₞౒ㅢᗵᨴ∝䈱ᗵᨴⅣ䈱଀㩷
㧟㧚Research projects and annual reports
㩷 ▵⿷േ‛ᇦ੺ᕈੱ₞౒ㅢᗵᨴ∝䈱଀䈫䈚䈩䇮Ⰶ䈏ᇦ੺䈜䉎
䉡䉣䉴䊃䊅䉟䊦䉡䉟䊦䉴ᗵ ᨴ∝ 䈱ᗵᨴ Ⅳ䉕␜䈜䇯⥄ὼ ⇇ 䈪䈲䇮
Ⰶ䈏ᇦ੺⠪㩿䊔䉪䉺䊷㪀䈫䈭䈦䈩䊃䊥䈱㑆䈪↢ᵴⅣ䈏⛽ᜬ䈘䉏䈩䈇
䉎䇯䈚䈎䈚䇮⓭⊒⊛䈮䉡䊙䉇䊑䉺䇮䊍䊃䈮ᗵᨴ䈚⣖Ἳ╬㊀◊䈭∝
⁁䉕ᒁ䈐⿠䈖䈜䇯㩷
Research projects
Many micro-organisms exist in natural environment.
Some of them infect to plants, and some do to animals
including human. They cause unique diseases to their
host plants and animals. However, the others do not.
Some are alive in animal intestine and help
(2) Molecular biology of the infection mechanisms of
mosquito- and tich-borne pathogens
food-digestion of host animals. Some are thought to play
important roles for host evolution. Microbes interact
Flavivirus is one of etiological agents of tick- and
with their host and establish micro- and macro-cosmos in
mosquito-borne diseases. The infection of the viruses
nature.
starts by attachment to cell surface receptor. However
We are now studying on pathology, ecology, and
the detail mechanisms of virus infection are still unclear.
other basic researches of zoonoses, especially, mosquito-
To study the first event of virus infection, we tried to
and tick-borne diseases. Recently, arthropod vectors are
identify the interaction partners against virus envelope
spreading their living places due to global warming.
protein, E, which is thought to be a virus-factor for
Therefore, the diseases become one of big concerns in
infection. We identified several candidates of host
world-wide public health. In Japan, it is also urgent to
factors for flavivirus infection. Now, we are confirming
establish a detection and prevention system for these
the actual interaction between viral E protein and
diseases.
candidate cellular proteins using molecular techniques.
Now, we are doing research on;
Mr. Igor and I are now doing research on this
(1) Epidemiological study on mosquito- and tick-borne
project.
diseases in Kyoto-City, and development of new
㩷
diagnostic and vaccine protocols for vector-borne
䋴䋮⺰ᢥ䋬⪺ᦠ䈭䈬㩷
diseases
Y. Makino, T. Suzuki, R. Hasebe, T. Kimura, A. Maeda, H.
(2) Molecular biology of the infection mechanisms of
Takahashi, H. Sawa: Establishment of tracking system for West
mosquito- and tick-borne pathogens
Nile virus entry and evidence of microtubule involvement in
particle transport. J. Vorol. Methods. 195, 250-257
Annual reports
A. Maeda, J. Maeda: Review of diagnostic plaque reduction
(1) Epidemiological study on mosquito- and
neutralization tests for flavivirus infection. Vet. J. 195, 33-40
tick-borne diseases in Kyoto-City, and
(review)
development of new diagnostic and vaccine
ᨴ⼱㩷 ᪧ, ᳰ᳗లብ, ᄢ⷏㩷 ୃ, Velado Fernandez Igor, ⷏㊁૫
એ, ೨↰⑺ᒾ: ੩ㇺᏒጊ⑼඙䈪㚟㒰䈘䉏䈢䉟䊉䉲䉲䈮ነ↢䈚䈩
protocols for vector-borne diseases
䈇䈢䊙䉻䊆㘃䈱⸃ᨆ. ੩ㇺ↥ᬺᄢቇ✚วቇⴚ⎇ⓥᚲᚲႎ . 8,
We collected mosquitoes, which are vectors of
many mosquito-borne diseases, at several fixed
57-62
observation points in Kyorto-City. We then tried to
೨↰⑺ᒾ: ╙4┨㩷 േ‛ᗵᨴ∝⸻ᢿ䈱䈢䉄䈱ᓸ↢‛ᬌᩏ䋬䋱䋮↥
detect pathogens within mosquitoes by molecular
ᬺേ‛䋬4)␹⚻♽ᗵᨴ∝.䋨✬䋩೽ᚲ⑺㓶䋬೨↰⑺ᒾ䉌 േ‛ᓸ
diagnostic protocol. As the result, we did not get any
↢‛ᬌᩏቇ 㩷 ㄭઍ಴ . pp.155-157
signs of infection of the pathogens within mosquitoes
㩷
captured in Kyoto City.
䋵䋮ቇળ⊒⴫䈭䈬㩷
We also conducted a tick-surveillance at north part
M. Yonejima, T. Nakaya, N. Nihei, Y. Tsuda, M. Kobayashi, M.
of Kyoto City. We collected many species of ticks, and
Watanabe, A. Maeda: Effects of land use pattern on spatial
tried to detect pathogens within ticks. We detected
distribution of host-seeking mosquitoes within urban areas in
several viruses by reverse transcription-polymerase
Kyoto, Japan. International Geographic Union䋬Kyoto Regional
reaction. Now, we would identify tick species and
Conference䋬kyoto, 2013.8.4-9
phylogenic analysis.
☨ፉਁ᦭ሶ, ೨↰⑺ᒾ, ⑔↰⟤᮸, દ⮮੝Ꮧ, Velado
We collaborated with Mr. Ikenaga, Mr. Ito, Miss
Fernandez Igor, ᵤ↰⦟ᄦ, ᷰㄝ㩷 ⼔, ਛ⼱෹᮸: ੩ㇺᏒ䈮䈍
Konno, and Miss Sugie in the㩷Kyoto City Institute of
䈔䉎䉝䉦䉟䉣䉦䈫䉼䉦䉟䉣䉦䈱᝝㓸ᢙ䈍䉋䈶᭴ᚑᲧ䈱ⓨ㑆Ꮕ⇣.
Health and environmental Sciences, Dr. Nakaya and
╙65࿁ᣣᧄⴡ↢േ‛ቇળᄢળ䋬ᳯ೎Ꮢ䋬2013.4.5-7
Miss Yoneshima in Ritsumeikan Universit䌹, and Dr.
Nihei in Asabu University.
દ⮮੝Ꮧ, ☨ፉਁ᦭ሶ, Velado Fernandez Igor, ⑔↰⟤᮸, ᨴ
⼱㩷 ᪧ, ೨↰⑺ᒾ: ੩ㇺᏒ䈮䈍䈔䉎Ⰶᇦ੺ᕈ䊐䊤䊎䉡䉟䊦䉴ᇦ
੺Ⰶ䈱⺞ᩏ. ╙48࿁ᣣᧄ⣖Ἳ䉡䉟䊦䉴↢ᘒቇ⎇ⓥળ䋬ᾲᶏᏒ䋬
2013.5.24-25
㩷
䋶䋮䈠䈱ઁ․⸥੐㗄㩷
䋱䋩㩷 ᄖㇱ⾗㊄
⑼ቇ⎇ⓥ⾌⵬ഥ㊄䊶᜸ᚢ⊛⪚⧘㩷
⺖㗴ฬ䋺䊐䊤䊎䉡䉟䊦䉴䈱ᗵᨴ⤳ེ․⇣ᕈ䈮㑐䈜䉎⎇ⓥ㩷
⎇ⓥઍ⴫⠪䋺೨↰⑺ᒾ㪃㩷 ขᓧᐕᐲ䋺㪟㪉㪋㪄㪉㪌 ᐕ㩷 㩿㪉 ᐕ㪀㩷
ෘ↢ഭ௛⑼ቇ⎇ⓥ⾌⵬ഥ㊄䋨ᣂဳ䉟䊮䊐䊦䉣䊮䉱╬ᣂ⥝䊶ౣ
⥝ᗵᨴ∝⎇ⓥ੐ᬺ䋩㩷
⺖㗴ฬ䋺∛ේ૕෸䈶Ქ⚛䈱▤ℂ䉲䉴䊁䊛䈍䉋䈶⹏ଔ䈮㑐䈜䉎
✚᜝⊛䈭⎇ⓥ䋨㪟㪉㪋㪄ᣂ⥝㪄৻⥸㪄㪇㪈㪊䋩㩷
⎇ⓥಽᜂ⠪䋺೨↰⑺ᒾ㪃㩷 ขᓧᐕᐲ䋺㪟㪉㪋㪄㪉㪍 ᐕ㩷 㩿㪊 ᐕ㪀㩷
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䋲䋩㩷 䈠䈱ઁ㩷 䈭䈚㩷
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Lab. Genetics in Experimental Medicine
Prof. Kozo Matsumoto, DVM, Ph.D
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human health in both developed and developing world.
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Common diseases such as type 2 diabetes mellitus result
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from complex interplay among multiple genes, signaling
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pathways and environmental factors. There are genetic
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analyses in human on genes extrapolated from the
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functional studies in vitro or in rodents in order to confirm
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the significance in the development of human diseases. Yet
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causative polymorphisms were still largely elusive. An
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alternative to the gene knockout model is the use of
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spontaneous animal models. The OLETF rat is such a
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model of obesity-based type 2 diabetes. Subsequently
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produced congenic strains showed that most of the loci
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examined were shown to contribute to the increased glucose
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levels in 30 week-old males. Interestingly, the phenotypic
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features observed in single congenic strain, low fat weight
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and low leptin levels for Nidd1/of and high fat weight for
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Nidd2/of, were masked in the double congenic, yet
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hyperglycemia were further aggravated than either single
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congenic strain. In order to investigate an affect of obesity
džDžªƬƀņIÎS;ĉƼ
to these loci, we have also generated a congenic strain
T<(džƥƲF-.şıƲK’ŠŽq’ě˜E
introgressed obesity gene (lpr deficiency). We have
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produced a double congenic line with a hyperglycemic gene
9(ŷ5DLJƥƲ(y’rŽELjƥƲě˜;]F(ě˜
(Nidd2, Nidd4, and Nidd6) under obesity condition by
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crossing both strains, so that it would be possible to define a
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gene specifically affecting hyperglycemia under obesity
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condition.
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1.
High Expression of Atp7b mRNA in the Peripheral
Blood Mononuclear Cells of the Long-Evans Cinnamon
Rats: an Animal Model of Wilson’s Disease. Kenji
Nakayama, Yoshinobu Katoh, Norikazu Shimizu, Toyo
Okui, Kozo Matsumoto, Yukiharu Sawada, Tsugutoshi
Aoki. Hereditary Genetics 2, 1-5, 2013
2.
Animal Models of Diabetes and Metabolic Disease.
Tomohiko Sasase, Marcus G. Pezzolesi, Norihide Yokoi,
Takahisa Yamada, and Kozo Matsumoto. J. Diabetes
Res. ID 281928, 1-2, 2013
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ᰤ㣴⾨⏕Ꮫ◊✲ᐊ㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌 㻌
z
㻌
㻸㼍㼎㼛㼞㼍㼠㼛㼞㼥㻌㼛㼒㻌㻺㼡㼠㼞㼕㼠㼕㼛㼚㻙㼞㼑㼘㼍㼠㼑㼐㻌㻴㼥㼓㼕㼑㼚㼑㻌 ᩍᤵ ᮧ⏣ ⱥ㞝㻌
Prof. Hideo Murata, D.V.M., Ph.D.㻌
㻌 䠍䠊◊✲ᴫせ㻌
㉁䛜Ꮡᅾ䛩䜛䛛ྰ䛛䛻䜘䛳䛶⏕䛨䛯䚹䛣䛾▱ぢ䛿᫖ᖺᗘ䛾◊
Ᏻ඲䛺㣗ᩱ䠄ື≀䛷䛿㣫ᩱ䠅䜢ᚓ䜙䜜䜛⏕ά⎔ቃ䛜䚸೺ᗣ
✲ሗ࿌䠄㼀㼍㼗㼟㼕㼚㼛㼞㼛㼟㻌㻒㻌㻹㼡㼞㼍㼠㼍䚸㻞㻜㻝㻞䠅䛸୍⮴䛧䛯䚹୍᪉䚸୧ΰ
䜢⥔ᣢ䛩䜛䛯䜑䛾᭱ప㝈୙ྍḞ䛺せ⣲䛷䛒䜛䛣䛸䛿ே䜒ື≀
࿴≀䛜 㻞㻜㻜䃛㼓㻛㼙㼘 ௨ୗ䛾⃰ᗘ䛷䛿䚸䝯䝷䝭䞁䝅䜰䝚䝺䞊䝖䛿㔪
䜒ྠ䛨䛷䛒䜛䚹䛭䛣䛷䚸ື≀་⛉Ꮫ䛾❧ሙ䛛䜙䚸㣫ᩱ䛾ෆᐜ
≧䚸⌫≧䛔䛪䜜䜒⏕ᡂ䛧䛺䛔䛣䛸䛜☜ㄆ䛥䜜䛯䚹䝯䝷䝭䞁ཬ䜃
䜔୚䛘᪉䚸䛩䛺䜟䛱ᰤ㣴⟶⌮䛜ዴఱ䛻ື≀䛯䛱䛾೺ᗣ䜢Ᏺ
䝅䜰䝚䝹㓟䛾⾑୰⃰ᗘ䛿䚸ື≀䜈䛾ᢞ୚ᐇ㦂䛷䛿 㻞㻜䃛㼓㻛㼙㼘
䜚䚸䜎䛯࿨䜢Ᏺ䜛䠄䛩䛺䜟䛱⾨⏕䠅௙⤌䜏䛻ᑐ䛧䛶䛹䛾䜘䛖䛻
⛬ᗘ䛸ሗ࿌䛥䜜䛶䛔䜛䛣䛸䛛䜙䚸䛚䛭䜙䛟ᚠ⎔⾑୰䜔⭈⮚௨
ᙳ㡪䛩䜛䛛䛻䛴䛔䛶䚸⏕యㄪ⠇ᶵᵓ䠄௦ㅰ䜔ච␿䠅䛾ື䛝䜢
እ䛾ㅖ⮚ჾ䛷䛿䚸䝯䝷䝭䞁䛸䝅䜰䝚䝹㓟䛜఍ྜ䛧䛶䜒⏕ᡂ≀䛿
┠༳䛸䛧䛶⛉Ꮫⓗ䛻⿬௜䛡䜛䛣䛸䜢◊✲┠ⓗ䛸䛩䜛䚹㻌
⏕䛨ᚓ䛪䚸⭈⮚䛾⃰⦰㐣⛬䛷༑ศ㔞䛾⃰ᗘ䛻㐩䛧䛯୧⪅䛜
ୖグ䛾୍⎔䛸䛧䛶䚸ᡃ䚻䛿䚸㐣ཤᩘᖺ㛫䛻ர䜚䚸㣫ᩱ䛻ΰ
ධ䛩䜛䜹䝡ẘ䛾ᙳ㡪䜔㝖ཤἲ䛻䛴䛔䛶◊✲䛧䚸ᡂᯝ䜢ㄽᩥ
཯ᛂ䛧䛶ึ䜑䛶⤖ᬗ䠄䛩䛺䜟䛱⤖▼䛾୺せᡂศ䠅䜢⏕ᡂ䛩䜛
䛾䛷䛿䛺䛔䛛䛸♧၀䛥䜜䛯䚹㻌
㻌
➼䛷㐺ᐅබ㛤䛧䛶䛝䛯䚹⌧ᅾ䛿䛭䛾◊✲᪉ྥ䜢Ⓨᒎ䛥䛫䚸᪂
䛯䛻㣗䞉㣫ᩱ୰䛾䝯䝷䝭䞁ởᰁ䛾ᙳ㡪䛻䛴䛔䛶◊✲䜢㐍䜑䛶
㻌
䛔䜛䚹ලయⓗ䛻䛿䚸㏆ᖺ䚸ங〇ရ䜔䝨䝑䝖䝣䞊䝗䜈䛾ΰධở
㻌
ᰁ䛻䜘䛳䛶኱䛝䛺♫఍ⓗᙳ㡪䜔୙Ᏻ䜢୚䛘䛯䝯䝷䝭䞁㢮䜢ᑐ
㻌
㇟䛻䛧䛶䚸ḟ䛾ㅖⅬ䛻䛴䛔䛶◊✲䜢ᒎ㛤䛩䜛䚹㻌
㻌
䠍䠅䝯䝷䝭䞁㞀ᐖస⏝䛾௙⤌䜏䛾ゎ᫂㻌
㻌
㻵㼚㻌 㼢㼕㼢㼛 ཬ䜃 㼕㼚㻌 㼢㼕㼠㼞㼛 ᐇ㦂䜢㏻䛧䛶䚸䝯䝷䝭䞁䛻䜘䜛䚸⭈⤌
㻌
⧊䜔ᶵ⬟䜢୺ᑐ㇟䛻䛧䛯ᶵ⬟㞀ᐖᶵᗎ䜢ゎ᫂䛩䜛䚹㻌
ᅗ䠖䝯䝷䝭䞁䝅䜰䝚䝺䞊䝖䠄ᕥ䠖㔪≧䛸ྑ䠖⌫≧⤖ᬗ䠅䛾ගᏛ㢧ᚤ㙾ീ㻌
䠎䠅⡆༢㻛Ᏻ౯㻛㎿㏿䛺䝯䝷䝭䞁㻙䝇䜽䝸䞊䝙䞁䜾ἲ䛾☜❧㻌
⾲ᒙ䛻㟷Ⰽ 㻳㻺㻼 䝬䞊䜹䞊䛜௜╔䛧䛶䛔䜛䠄ⓑ▮༳䠅㻌
⏕⏘䞉ὶ㏻䛒䜛䛔䛿ᾘ㈝⌧ሙ䛷䜒⡆༢䞉Ᏻ౯䛛䛴⣲᪩
䛟⾜䛘䜛䝇䜽䝸䞊䝙䞁䜾᳨ฟἲ䛾☜❧䜢┠ᣦ䛩䚹㻌
䠄䝇䜿䞊䝹䝞䞊䛿 㻞㻚㻡䃛㼙䠅㻌
㻌
㻌
䠎䠅⡆᫆䞉㎿㏿䛺䝯䝷䝭䞁䝇䜽䝸䞊䝙䞁䜾ἲ䛾☜❧㻌
䠎䠊ᮏᖺᗘ䛾◊✲ᡂᯝ㻌
㻌 ᮏᖺᗘ䛿ᐇ᪋䛧䛺䛛䛳䛯䚹ḟᖺᗘ௨㝆䛻ㄢ㢟䜢⥅⥆䛩䜛䚹㻌
䠍䠅䝯䝷䝭䞁㞀ᐖస⏝䛾௙⤌䜏㻌
㻌
㣗ရ䜔㣫ᩱ୰䛻ΰධ䛧䛯䝯䝷䝭䞁䛜䚸ᾘ໬⟶䛛䜙యෆ䛻྾
㸱㸬Research projects and annual reports
཰䛥䜜ᚠ⎔⣔䜢⤒⏤䛧䛶᤼ἥ䛻⮳䜛㐣⛬䛷䚸㢮ఝᵓ㐀య䛾
As well as humans, all human-associated animals, including
୍䛴䛷䛒䜛䝅䜰䝚䝹㓟䛸཯ᛂ䛧䚸⭈⮚䛷⤖▼໬䛧䚸㔜⠜䛺⭈
livestock, companion and experimental animals, have the
㞀ᐖ䜢䜒䛯䜙䛩䛣䛸䛜᪤䛻ሗ࿌䛥䜜䛶䛔䜛䚹䛭䛾୺せᵓᡂ≀
same right to acquire safe aliment to maintain their healthy
䝯䝷䝭䞁䝅䜰䝚䝺䞊䝖䛾⏕ᡂ䛿 㼕㼚㻌 㼢㼕㼠㼞㼛 ୗ䛷䜒ᐜ᫆䛻෌⌧䛷䛝
conditions, thereby contributing to humans. As researchers in
䜛䛜䚸ᐇ㝿䛾⤖▼Ⓨ⑕౛䠄㼕㼚㻌 㼢㼕㼢㼛䠅䛷䛿䚸⭈⮚䛾䝛䝣䝻䞁㒊఩
veterinary medical science, we have been interested in
௨እ䛷䛾Ꮡᅾ䛿☜ㄆ䛥䜜䛶䛔䛺䛔䚹䛭䛾⌮⏤䛿䜎䛰᫂䜙䛛
detecting and reducing feed contaminants that could harm
䛷䛿䛺䛔䛜䚸཯ᛂ᫬䛾䝯䝷䝭䞁䛸䝅䜰䝚䝹㓟䛾⃰ᗘせᅉ䛜㛵
animal health. Our present research purpose is to (1) elucidate
୚䛧䛶䛔䜛ྍ⬟ᛶ䛜䛒䜛䚹௒ᖺᗘ䛿䚸䛭䛾ྍ⬟ᛶ䜢 㼕㼚㻌 㼢㼕㼠㼞㼛
the adverse effects of melamine, a toxic chemical that could
ᐇ㦂䛷᳨ド䛧䛯䚹㻌
cause kidney stones and kidney failure when ingested, through
㻞㻜䡚㻝㻜㻜㻜䃛㼓㻛㼙㼘 䛻ㄪᩚ䛧䛯䝯䝷䝭䞁䛸䝅䜰䝚䝹㓟䜢ΰ࿴
䠄ྠ୍⃰ᗘ䛷➼㔞䠅䛧䚸䛭䛾⏕ᡂ≀䛾Ꮡᅾ䜔ᙧ≧䜢 㼓㼛㼘㼐㻌
㼚㼍㼚㼛㼜㼍㼞㼠㼕㼏㼘㼑㻔㻳㻺㻼㻕㻌 ྠᐃᡭἲ䠄㻸㼕 䜙䚸㻞㻜㻝㻜䠅䜢⏝䛔䛶䚸ගᏛ㢧
ᚤ㙾䛷ほᐹ䛧䛯䚹䝯䝷䝭䞁䝅䜰䝚䝺䞊䝖䛿䚸䛭䛾⾲ᒙ䛜㟷Ⰽ䜢
࿊䛩䜛 㻳㻺㻼 䛷そ䜟䜜䛯㔪≧䛒䜛䛔䛿⌫≧⏕ᡂ≀䛸䛧䛶ほᐹ
䛥䜜䛯䠄ᅗ䠅䚹䛣䛾ᙧ≧䛾㐪䛔䛿䚸ΰ࿴⎔ቃෆ䛻⾑Ύ䝍䞁䝟䜽
in vivo and in vitro studies, and (2) establish a rapid, easy and
cheap melamine screening method.
The results obtained this year are summarized as follows:
1: On the threshold concentrations of melamine and cyanuric
acid for formation of melamine-cyanurate crystals:
The crystals accumulate as urolites but are not found outside
ᰤ㣴⾨⏕Ꮫ◊✲ᐊ䛾ᵓᡂ䠄䠎䠌䠍䠐ᖺ䠏᭶⌧ᅾ䠅
the urinary system. In this in vitro experiment we found that
኱Ꮫ㝔༤ኈᚋᮇㄢ⛬Ꮫ⏕㻌 䠍ྡ
M-C crystals were not formed in a mixture of melamine and
Ꮫ㒊䠐ᖺ⏕㻌 䠐ྡ
cyanuric acid at low concentrations (< 200 μg/ml). The results
Ꮫ㒊䠏ᖺ⏕㻌 䠏ྡ
suggest that the plasma melamine and cyanuric acid
concentrations reported in clinical cases would be too low to
form and/or accumulate M-C crystals in the bloodstream, thus
S. Taksinoros 䠄኱Ꮫ㝔⏕䠅 䛸ᮧ⏣
explaining why the crystals are not detected outside the
urinary organs in affected humans and animals.
2: Development of a melamine screening method
No substantial experiments on this theme have been carried
out this year.
䠐䠊ㄽᩥ䚸ⴭ᭩䛺䛹㻌
S. Taksinoros, H. Murata,: Effects of polyvinylpyrrolidone on in vitro
melamine cyanurate crystal formation: An electron microscopy
study. 2013. J. Vet. Med. Sci., 75, 653-655
㻡䠊Ꮫ఍Ⓨ⾲䛺䛹㻌 㻌
䛺䛧㻌
䠒䠊䛭䛾௚≉グ஦㡯㻌
㸯㸧እ㒊㈨㔠
䛺䛧㻌
㸰㸧Ꮫእάື㻌
㻌 㻌 㻌 The Veterinary Journal ㄅ䛾 Editorial Advisory ጤဨ
㻌 㻌 ி㒔ື≀ឡㆤ䝉䞁䝍䞊䠄௬⛠䠅㐠Ⴀጤဨ
䠏䠅㻌 䛭䛾௚㻌
㻌 ி㒔⏘ᴗ኱Ꮫ 㻰㻭㼅㻌㼕㼚 బ㈡㻌 䛷䛾ㅮ₇㻌 㻌
䛂ື≀䛯䛱䜈䛾㓄៖䠄ឡㆤ䛸⚟♴䠅䛃䠄㻞㻜㻝㻟㻚㻜㻤㻚㻞㻠䠅㻌
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ᾁ ὿ ᾀ ᾂ ࠰ᴾ
ዮӳဃԡᅹ‫ܖ‬ᢿᴾ
ᄂ ᆮ Ἒ ἦ ἕ ἁ Ἃᴾ
研究トピックス（１）：バイオフォーラムなどのセミナー開催状況
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研究トピックス（１）：バイオフォーラムなどのセミナー開催状況
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