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中枢シナプス生後発達分化の細胞分子メカニズム

Research Project

Project/Area Number 13002004
Research Category

Grant-in-Aid for Specially Promoted Research

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionThe University of Tokyo

Principal Investigator

高橋 智幸  東大, 医学(系)研究科(研究院), 教授 (40092415)

Co-Investigator(Kenkyū-buntansha) 辻本 哲宏  東京大学, 大学院・医学系研究科, 講師 (40212055)
齋藤 直人 (斎藤 直人)  東京大学, 大学院・医学系研究科, 助手 (90334226)
Project Period (FY) 2001 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥538,200,000 (Direct Cost: ¥414,000,000、Indirect Cost: ¥124,200,000)
Fiscal Year 2005: ¥80,600,000 (Direct Cost: ¥62,000,000、Indirect Cost: ¥18,600,000)
Fiscal Year 2004: ¥85,800,000 (Direct Cost: ¥66,000,000、Indirect Cost: ¥19,800,000)
Fiscal Year 2003: ¥91,000,000 (Direct Cost: ¥70,000,000、Indirect Cost: ¥21,000,000)
Fiscal Year 2002: ¥115,700,000 (Direct Cost: ¥89,000,000、Indirect Cost: ¥26,700,000)
Fiscal Year 2001: ¥165,100,000 (Direct Cost: ¥127,000,000、Indirect Cost: ¥38,100,000)
Keywords生後発達 / シナプス / AMPA受容体 / ダイナミン / エンドサイトーシス / NCS-1 / cAMP / Caチャネル / K電流 / シナプス可塑性 / アデノシン / レセプター飽和 / 微小シナプス電流 / 神経終末端 / シナプス小胞 / Ca電流 / シナプス増強 / グルタミン酸 / シプナス / 伝達効率 / calyx of Held / PKC / Gタンパク質 / レセプター
Research Abstract

(1)生後発達に伴う興奮性シナプス応答時間短縮におけるAMPA型グルタミン酸受容体サブユニットの役割:単一細胞RT-PCR法を用いて、生後発達に伴うAMPA受容体電流脱感作時間の短縮にGluR4 flopの発現増加が寄与することを明らかにした。また、生後発達に伴うAMPA受容体媒介性シナプス電流下降相の短縮にはAMPA受容体チャネルの脱感作時間の短縮と共に、開口時間の短縮が関与することが明らかになった。(Koike-Tani et al 2005 J Neurosci)。
(2)神経終末端シナプス小胞の回収に関与するGタンパク質:聴覚中継シナプスcalyx of Heldにおけるendocytosisは専ら単量体Gタンパク質dynaminに依存することが明らかになった(Yamashita et al,2005 Science)。
(3)神経終末端Ca電流の活動依存性増強分子機構:Ca電流の活動依存性増強はCa結合タンパク質NCS-1によって媒介されることを以前に報告したが、NCS-1依存性のCa電流増強はP/Q型Caチャネル特異的で、シナプス伝達の増強に寄与することが明らかになった(Ishikawa et al 投稿中)。
(4)cAMP依存性シナプス増強分子機構:神経末端のcAMP濃度が上昇すると伝達物質の放出が増強されることを直接的に証明した。更に、この作用はAkinaseに依存せず、cAMP-GEF (Epac)に依存性することが明らかになった(Kaneko et al,2004 J Neurosci)。
(5)神経終末端Caチャネルサブタイプの生後発達スイッチを制御する分子機構の解明:Caチャネルサブユニットの選別分子機構に関して、Caチャネルのα_1サブユニットに特異的に結合する新たなタンパク質を2種類見出した、そのうちのひとつはN型Caチャネルα_<1B>サブユニットに特異的な結合を示した(未発表)。

Report

(4 results)
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (19 results)

All 2005 2004 Other

All Journal Article (6 results) Publications (13 results)

  • [Journal Article] Dynamic aspects of presynaptic calcium currents mediating synaptic transmission2005

    • Author(s)
      Tomoyuki Takahashi
    • Journal Title

      Cell Calcium (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Vesicle endocytosis requires dynamin-dependent GTP hydrolysis at a fast CNS synapse2005

    • Author(s)
      Yamashita T., Hige T., Takahashi T
    • Journal Title

      Science 307

      Pages: 124-127

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Presynaptic mechanism underlying cAMP-dependent synaptic potentiation2005

    • Author(s)
      Koike-Tani M., Saitoh N., Takahashi T
    • Journal Title

      J.Neurosci. 25

      Pages: 199-207

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Presynaptic mechanism underlying cAMP-dependent synaptic potentiation2004

    • Author(s)
      Kaneko M., Takahashi T.
    • Journal Title

      J.Neurosci. 24

      Pages: 5202-5208

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Presynaptic mechanism underlying regulation of transmitter replase by G protein coupled receptors2004

    • Author(s)
      Takahashi T., Kajikawa Y., Kimura M., Saito N., Tsujimoto T.
    • Journal Title

      Korean, J.of Physiol.Pharmacol. 8

      Pages: 69-76

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Voltage-activated Ca2+ channels and their role in the endocrine function of the pituitary gland in newborn and adult mice2004

    • Author(s)
      Sedej S., Tsujimoto T., ZXorec R., Rupnik M.
    • Journal Title

      J.Physiol. 555

      Pages: 769-782

    • Related Report
      2004 Annual Research Report
  • [Publications] Kimura M., Saitoh N., Takahashi T.: "Adenosine A_1 receptor-mediated presynaptic inhibition at the calyx of Held of immature rats"J Physiol.. 553. 415-426 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishikawa T., Nakamura Y., Saitoh N., Li W.B., Iwasaki S., Takahashi T.: "Distinct roles of Kv1 and Kv3 potassium channels at the calyx of Held presynaptic terminal"J.Neurosci.. 23. 10445-10453 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Mori-Kawakami F., Kobayashi K., Takahashi T.: "Developmental decrease in synaptic facilitation at the mouse hippocampal mossy fiber synapse"J Physiol.. 553. 37-48 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yamashita T., Ishikawa T., Takahashi T.: "Developmental increase in vesicular glutamate content dose not cause saturation of AMPA receptors at the calyx of Held synapse"J.Neurosci.. 23. 3633-3638 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Tsujimoto T, Jeromin A, Saitoh N, Roder JC, Takahashi T: "Neuronal calcium sensor 1 and activity-dependent facilitation of P/Q-type calcium currents at presynaptic nerve terminals"Science. 275. 2276-2279 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishikawa T, Sahara Y, Takahashi T: "A single packet of transmitter does not saturate postsynaptic glutamate receptors"Neuron. 34. 613-621 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamashita T, Ishikawa T, Takahashi T: "Developmental increase in vesicular glutamate content does not cause saturation of AMPA receptors at the calyx of Held synapse"J. Neurosci. (in press). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Futai K. et al.: "High-fidelity transmission acquired via a developmental decrease in NMDA receptor expression at an auditory synapse"J. Neurosci. 21. 3342-3349 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishikawa T., Takahashi T.: "Mechanisms underlying presynaptic facilitatory effect of cyclothiazide at the calyx of Held of juvenile rats"J. Physiol. 533. 423-431 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Kajikawa Y. et al.: "GTP-binding protein βγsubunits mediate presynaptic calcium current inhibition by GABA_B receptor"Proc. Natl. Sci. USA. 98. 8054-8058 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Iwasaki S., Takahashi T.: "Developmental regulation of transmitter release at the calyx of Held in rat auditory brainstem"J. Physiol. 534. 861-871 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sahara Y., Takahashi T.: "Quantal components of the excitatory postsynaptic currents at a rat central auditory synapse"J. Physiol. 536. 189-197 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Saitoh N. et al.: "Activation of the epsilon isoform of protein kinase C in the mammalian nerve terminal"Proc. Natl. Sci. USA. 98. 14017-14021 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2018-03-28  

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