Roles and modes of action of tomosyn in neurotransmitter release

• Project/Area Number: 19500322
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Kobe University
• Principal Investigator: SAKISAKA Toshiaki Kobe University, 大学院医学研究科, 教授 (80359843)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: 神経伝達物質の放出機構 / SNARE複合体 / トモシン

Research Abstract

神経細胞が次の神経細胞に情報を伝えるシナプス伝達の主たる過程は、神経伝達物質の放出により行われている。従って、神経伝達物質の放出の過程を解明していくことは、シナプスの可塑性ひいては記憶形成の過程を理解する上で重要である。これまで、私共は、神経伝達物質の放出にSNARE系の活性制御タンパク質であるトモシンが抑制的に働くことを明らかにしている。トモシンがt-SNAREsとトモシン複合体を形成し、小胞融合に必須なSNARE複合体の形成を抑制することにより、神経伝達物質の放出を制御している。このトモシンの生体での機能を明らかにするために、トモシンノックアウトマウスを作成し、トモシンの生理的作用について解析した。その結果、トモシンが、SNARE複合体の多量体化の促進とSNARE複合体形成の抑制の二つの作用を介して、強力に神経伝達物質の放出を抑制することを明らかにした。

Research Products

• [Journal Article] Reciprocal intramolecular interactions of tomosyn control its inhibitory activity on the SNARE complex formation. (2009)
  • Author(s): Yamamoto, Y., Mochida, S., Kurooka, T., and Sakisaka, T.
  • Journal Title: J. Biol. Chem. in press Pages: 0-0
  • Peer Reviewed
• [Journal Article] Cell Adhesion Molecules in the Central Nervous System (2009)
  • Author(s): Togashi, H., Sakisaka, T., and Takai, Y.
  • Journal Title: Cell Adhesion & Migration, in press Pages: 0-0
  • Peer Reviewed
• [Journal Article] Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release (2008)
  • Author(s): Sakisaka, T., Yamamoto, Y., Mochida, S., 他8名
  • Journal Title: J. Cell Biol. 183巻 Pages: 323-337
  • Peer Reviewed
• [Journal Article] A cell-free assay for endocytosis of E-cadherin. (2008)
  • Author(s): Sakisaka, T., and Takai, Y.
  • Journal Title: Methods Mol Biol. 440巻 Pages: 77-87
  • Peer Reviewed
• [Journal Article] Dual inhibition of SNARE complex formation by tomosyn ensures controlled neurotransmitter release. (2008)
  • Author(s): Toshiaki Saklsaka
  • Journal Title: The Journal of Cell Biology 183 Pages: 323-337
  • Peer Reviewed
• [Journal Article] A cell-free assay for endocytosis of E-cadherin. (2008)
  • Author(s): Toshiakl Sakisaka
  • Journal Title: Methods in Molecular Biology 440 Pages: 77-87
  • Peer Reviewed
• [Journal Article] The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors. (2007)
  • Author(s): Sakisaka, T., Ikeda, W., Ogita, H., 他2名
  • Journal Title: Curr. Opin. Cell Biol. 19巻5号 Pages: 0-0
  • Peer Reviewed
• [Journal Article] Rap1-PDZ-GEF interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. (2007)
  • Author(s): Hisata, S., Sakisaka, T., Baba, T., 他4名
  • Journal Title: J. Cell Biol. 178巻5号 Pages: 843-860
• [Journal Article] Rap1-PDZ-GEF interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth (2007)
  • Author(s): Hisata, S.
  • Journal Title: J. Cell Biol. 178-5 Pages: 843-860
  • Peer Reviewed
• [Journal Article] The roles of nectins in cell adhesions: cooperation with other cell adhesion molecules and growth factor receptors (2007)
  • Author(s): Sakisaka, T.
  • Journal Title: Curr. Opin. Cell Biol. 19-5 Pages: 593-602
  • Peer Reviewed
• [Presentation] Vesicle transport-dependent Rap1 activation and its implication in neurite outgrowth (2008)
  • Author(s): Toshiaki Sakisaka, Yoshimi Takai
  • Organizer: BMB2008
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2008-12-09
• [Presentation] Vesicle transport-dependent Rap1 activation and its implication inneurite outgrowth (2008)
  • Author(s): Toshiaki Sakisaka
  • Organizer: BMB2008
  • Place of Presentation: 神戸国際展示場
  • Year and Date: 2008-12-09
• [Presentation] 小胞輸送によるRap1の活性化機構と軸索形成への関与 (2007)
  • Author(s): 匂坂 敏朗、高井 義美
  • Organizer: 第40回日本発生生物学会・第59回日本細胞生物学会 合同大会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2007-05-30
• [Remarks] ホームページ等
  • URL: http://www.med.kobe-u.ac.jp/membrd/