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神経回路強化に関わるシナプス前終末カルシウムチャネルの機能解析

Research Project

Project/Area Number 20021025
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTokyo Medical University

Principal Investigator

持田 澄子  Tokyo Medical University, 医学部, 教授 (30096341)

Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2009: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2008: ¥3,500,000 (Direct Cost: ¥3,500,000)
KeywordsCa^<2+>チャネル / シナプス前終末 / シナプス可塑性 / カルモジュリン依存性燐酸化酵素 / シナプス伝達 / 神経回路 / シナプス / カルシウムチャネル
Research Abstract

脳由来P/Q型Ca^<2+>チャネルα1サブユニットをシナプス前細胞に発現させ、脳由来CaMKII阻害ペプチド(CaM-KIIN)を共発現したシナプス、α1サブユニットのCaMKIIと結合する部分ペプチド(Ca_V2.1_<1897-1912>)、あるいはCaMKII活性化阻害ペプチド(AIP)をシナプス前細胞へ注入したシナプスでのCa^<2+>チャネルの活性化パターンの違いによる神経伝達物質放出の変化を電気生理学的手法で解析して、下記の(1)-(4)が明らかとなった。
(1)Paired-pulse depressionとfacilitationは、CaM-KIINを共発現、あるいはCa_V2.1_<1897-1912>を導入したシナプスで抑制される。
(2)高頻度発火によるsynaptic depressionは、CaM-KIINを共発現、あるいはCa_V2.1_<1897-1912>を導入したシナプスで減弱し、synaptic facilitationが認められる。
(3)Augmentationは、CaM-KIINを共発現、あるいはCa_V2.1_<1897-1912>を導入したシナプスで顕著に抑制されるが、PTPは影響を受けない。
(4)AIP導入したシナプスでは、コントロールシナプスと同程度のsynaptic depression、augmentation PTPを誘起する。
すなわち、CaMKIIの蛋白燐酸化過程を介するのではなく、CaMKIIがシナプス前終末Ca^<2+>チャネルに結合して、そのCa^<2+>チャネルの活性を高めることを示唆する。このようにして神経活動によって流入するCa^<2+>量を制御するCaMKIIは、Ca^<2+>濃度に依存して活性化されるCaMによるCa^<2+>チャネル活性調節を伴う短期可塑性や、各種のシナプス前神経終末Ca^<2+>結合蛋白質を介したシナプス伝達亢進をもたらすと考えられ、"effecter checkpoint"としての機能を果たす。

Report

(2 results)
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (18 results)

All 2010 2009 2008 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results) Presentation (9 results) Book (1 results) Remarks (1 results)

  • [Journal Article] Reciprocal intramolecular interactions of tomosyn control inhibition of the SNARE complex formation.2009

    • Author(s)
      Yamamoto,Y., 他3名
    • Journal Title

      J Biol Chem. 284(18)

      Pages: 12480-12490

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] KIF5B Motor Adaptor Syntabulin Maintains Synaptic Transmissionin Sympathetic Neurons.2009

    • Author(s)
      Ma,H., 他4名
    • Journal Title

      J.Neurosci. 29(41)

      Pages: 13019-13029

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Glutamate receptor, Munc18-1 and calmodulin detect Ca^<2+> to regulate synaptic transmission.2009

    • Author(s)
      Nakajima,Y., 他3名
    • Journal Title

      Proc.Natl.Acad.Sci.USA 106(43)

      Pages: 18385-18389

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamin and activity regulate synaptic vesicle recycling in sympathetic neurons2009

    • Author(s)
      Lu, W
    • Journal Title

      J Biol Chem 284

      Pages: 1930-1937

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Reciprocal intramolecular interactions of tomosyn control inhibition of the SNAR E complex formation2009

    • Author(s)
      Yamamoto, Y
    • Journal Title

      J Biol Chem Mar 3. [Epub ahead of print]

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dual inhibition of SNARE complex formation by tomosyn ensures controlled neu rotransmitter release2008

    • Author(s)
      Sakisaka, T
    • Journal Title

      J Cell Biol 183(2)

      Pages: 323-337

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 神経伝達物質の放出機構2008

    • Author(s)
      持田澄子
    • Journal Title

      日本生理学雑誌 70

      Pages: 78-86

    • NAID

      10024918906

    • Related Report
      2008 Annual Research Report
  • [Presentation] Mechanisms of Exocytosis at a Cholinergic Nerve Terminal2010

    • Author(s)
      Mochida, S.
    • Organizer
      Research Workshop on MECHANISMS of EXOCYTOSIS
    • Place of Presentation
      Jerusalem
    • Year and Date
      2010-03-08
    • Related Report
      2009 Annual Research Report
  • [Presentation] モデルシナプスを用いた神経伝達物質放出機序の解析2009

    • Author(s)
      持田澄子
    • Organizer
      「社会性認識」学際脳科学シンポジウム
    • Place of Presentation
      金沢
    • Year and Date
      2009-11-06
    • Related Report
      2009 Annual Research Report
  • [Presentation] V-ATPase membrane sector associates with synaptobrevin to mediate neurotransmitter release2009

    • Author(s)
      El Far, O., 他11名
    • Organizer
      38^<th> Annual meeting of the Soc. for Neuroscience
    • Place of Presentation
      Chicago
    • Year and Date
      2009-10-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] Probing the molecular determination of G protein beta gamma subunit-mediated modulation of presynaptic calcium channels in superior cervical ganglion nearons.2009

    • Author(s)
      Bucci, G., Mochida, S., Stephens, G.
    • Organizer
      38^<th> Annual meeting of the Soc. for Neuroscience
    • Place of Presentation
      Chicago
    • Year and Date
      2009-10-20
    • Related Report
      2009 Annual Research Report
  • [Presentation] Presynaptic Molecular Regulation for Transmitter Release2009

    • Author(s)
      Mochida,S.
    • Organizer
      IUPS 2009 WD-7 SYMPOSIUM
    • Place of Presentation
      京都
    • Year and Date
      2009-07-29
    • Related Report
      2009 Annual Research Report
  • [Presentation] Activity-dependent and-independent synaptic vesicle recycling in sympa thetic neurons2008

    • Author(s)
      Mochida, S
    • Organizer
      38^<th> Annual meeting of the Soc. for Neuroscienc
    • Place of Presentation
      Washigton, DC
    • Year and Date
      2008-11-16
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation pf Presynaptic Cav2.1 channels by Ca2+ Sensor Proteins Me diates Short-term Synaptic Plasticity2008

    • Author(s)
      Mochida, S
    • Organizer
      COE International Symposium 2008 on Developm ent, Learning, Memory and Autism
    • Place of Presentation
      金沢
    • Year and Date
      2008-07-17
    • Related Report
      2008 Annual Research Report
  • [Presentation] Transpot of mitochondria to presynaptic terminals by syntabulin is requ ired for synaptic transmission2008

    • Author(s)
      Mochida, S
    • Organizer
      Neuro 2008
    • Place of Presentation
      東京
    • Year and Date
      2008-07-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] Regulation pf Presynaptic Cav2.1 channels by Ca2+ Sensor Proteins Me diates Short-term Synaptic Plasticity2008

    • Author(s)
      Mochida, S
    • Organizer
      Gordon Reshearch Conference Cell Biology of the Neuron
    • Place of Presentation
      New London, USA
    • Year and Date
      2008-06-16
    • Related Report
      2008 Annual Research Report
  • [Book] ニューロンの生理学2009

    • Author(s)
      D. Thtsch(編)
    • Total Pages
      759
    • Publisher
      京都大学学術出版会
    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

      http://www.tokyo-med.acjp/physiol/Pub2.html

    • Related Report
      2009 Annual Research Report

URL: 

Published: 2008-04-01   Modified: 2018-03-28  

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