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The endosomal Q-SNARE, Syntaxin 7, defines a rapidly replenishing synaptic vesicle recycling pool in hippocampal neurons

Research Project

Project/Area Number 18K06473
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46010:Neuroscience-general-related
Research InstitutionDoshisha University

Principal Investigator

Yasunori Mori  同志社大学, 研究開発推進機構, 准教授 (80443042)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Keywords神経 / シナプス / シナプス小胞 / 小胞輸送 / ライブイメージング / SNARE / カルシウム / アクチン / シナフス小胞 / エンドソーム / 軸索前終末 / ライブイメージ / プレシナプス / SNAREタンパク質 / シナプス小胞プール
Outline of Final Research Achievements

Replenishment of readily releasable synaptic vesicles (SVs) with vesicles in the recycling pool is important for sustained transmitter release during repetitive stimulation. However, whether all SVs in the recycling pool are recruited for release with equal probability and speed is unknown. Here, using comprehensive optical imaging of various presynaptic endosomal SNARE proteins in cultured hippocampal neurons, we demonstrate that part of the recycling pool bearing the endosomal Q-SNARE, syntaxin 7 (Stx7), is preferentially mobilized for release during high-frequency repetitive stimulation. Recruitment of the SV pool marked with an Stx7-reporter requires actin polymerization, as well as activation of the Ca2+/calmodulin signaling pathway. Our data indicate that endosomal membrane fusion involving Stx7 forms rapidly replenishing vesicles essential for synaptic responses to high-frequency repetitive stimulation.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果として、これまでの研究では明らかにできなかったシナプス小胞プールを細分化する分子基盤を提唱し、シナプス前終末における神経伝達物質の多様な開口放出機構を明らかにすることができた。また、本研究により明らかになったシナプス小胞プールの違いを支える分子基盤は、一般的な小胞膜輸送に関わる基礎的な知見にも貢献することができた。本研究で得られた基礎的な知見は、シナプス伝達の異常が原因となる神経疾患に対する新しい治療戦略への波及が期待される。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (20 results)

All 2020 2019 2018 Other

All Journal Article (5 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 4 results,  Open Access: 5 results) Presentation (12 results) (of which Int'l Joint Research: 3 results) Remarks (3 results)

  • [Journal Article] Hidden proteome of synaptic vesicles in the mammalian brain2020

    • Author(s)
      Taoufiq Zacharie、Ninov Momchil、Villar-Briones Alejandro、Wang Han-Ying、Sasaki Toshio、Roy Michael C.、Beauchain Francois、Mori Yasunori、Yoshida Tomofumi、Takamori Shigeo、Jahn Reinhard、Takahashi Tomoyuki
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 52 Pages: 33586-33596

    • DOI

      10.1073/pnas.2011870117

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Q-SNARE Syntaxin 7 confers actin-dependent rapidly replenishing synaptic vesicles upon high activity2020

    • Author(s)
      Mori Yasunori、Takenaka Koichiro、Fukazawa Yugo、Takamori Shigeo
    • Journal Title

      BioRxiv

      Volume: 2020.08.13.

    • DOI

      10.1101/2020.08.13.249672

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Expression of plasma membrane calcium ATPases confers Ca2+/H+ exchange in rodent synaptic vesicles2019

    • Author(s)
      Ono Yoshiyasu、Mori Yasunori、Egashira Yoshihiro、Sumiyama Kenta、Takamori Shigeo
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 1-17

    • DOI

      10.1038/s41598-019-40557-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of lentiviral vectors for efficient glutamatergic-selective gene expression in cultured hippocampal neurons2018

    • Author(s)
      Egashira Yoshihiro、Mori Yasunori、Yanagawa Yuchio、Takamori Shigeo
    • Journal Title

      Scientific Reports

      Volume: 8 Issue: 1 Pages: 1-13

    • DOI

      10.1038/s41598-018-33509-5

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Molecular Signatures Underlying Synaptic Vesicle Cargo Retrieval2018

    • Author(s)
      Mori Yasunori、Takamori Shigeo
    • Journal Title

      Front Cell Neurosci

      Volume: 11 Pages: 422-422

    • DOI

      10.3389/fncel.2017.00422

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cargo-selective sorting function of clathrin adaptor protein AP-2 during clathrin-independent endocytosis at hippocampal synapses2020

    • Author(s)
      Koichiro Takenaka, Tania Lopez-Hernandez, Yasunori Mori, Shushi Nagamori, Volker Haucke, Shigeo Takamori
    • Organizer
      第72回 日本細胞生物学会 2020年6月9日
    • Related Report
      2020 Annual Research Report
  • [Presentation] A liquid phase of Intersectin1 serves as the cytoplasmic reservoir for endocytic proteins2020

    • Author(s)
      吉田知史, 竹中康一郎, 塙(末次)京子, 森靖典, 高森茂雄
    • Organizer
      第72回 日本細胞生物学会 2020年6月9日
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cargo-selective sorting function of clathrin adaptor protein AP-2 during clathrin-independent endocytosis at hippocampal synapses2020

    • Author(s)
      Koichiro Takenaka, Tania Lopez-Hernandez, Yasunori Mori, Shushi Nagamori, Volker Haucke, Shigeo Takamori
    • Organizer
      シナプス研究会2020 2020年12月3日
    • Related Report
      2020 Annual Research Report
  • [Presentation] 形質膜に係留されている ITSN1 によって形成される相分離環境はエンドサイトーシス関連タンパク質の動的な貯蔵庫として機能する2020

    • Author(s)
      吉田知史, 竹中康一郎, 塙(末次)京子, 森靖典, 高森茂雄
    • Organizer
      シナプス研究会2020 2020年12月3日
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cargo-selective sorting function of clathrin adaptor protein AP-2 during clathrin-independent endocytosis at hippocampal synapses2020

    • Author(s)
      Koichiro Takenaka, Tania Lopez-Hernandez, Yasunori Mori, Shushi Nagamori, Volker Haucke, Shigeo Takamori
    • Organizer
      JSPS Core-to-core Program (A) Symposium “Nanobiology of neural plasticity based on optical nanoscopy” 2020年12月9日
    • Related Report
      2020 Annual Research Report
  • [Presentation] Intersectin 1 condensates, the reservoir for various endocytic proteins, are anchored at plasma membrane by SNAP-252020

    • Author(s)
      Tomofumi Yoshida, Kohichiro Takenaka, Kyoko Hanawa-Suetsugu, Yasunori Mori, Shigeo Takamori
    • Organizer
      JSPS Core-to-core Program (A) Symposium “Nanobiology of neural plasticity based on optical nanoscopy” 2020年12月9日
    • Related Report
      2020 Annual Research Report
  • [Presentation] 神経終末におけるSyntaxin 7を含むシナプス小胞の機能解析2019

    • Author(s)
      森靖典, 竹中康一郎, 深澤有吾, 高森茂雄
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] 森靖典, 竹中康一郎, 深澤有吾, 高森茂雄2019

    • Author(s)
      Q-SNARE Syntaxin 7 defines a reluctant recycling pool of synaptic vesicles in hippocampal neurons
    • Organizer
      生理学研究所シナプス研究会「ミクロからマクロに至る脳の構造と機能のダイナミクス」
    • Related Report
      2019 Research-status Report
  • [Presentation] Endosomal Q-SNARE Syntaxin-7 specifies a subpopulation of recycling synaptic vesicles preferentially responsive to high frequency stimulation.2018

    • Author(s)
      Mori Y, Fukazawa Y, Takamori S.
    • Organizer
      Joint annual meeting of 51st JSDB and 70th JSCB.
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 海馬培養神経細胞で興奮性ニューロン選択的に遺伝子発現を誘導するレンチウイルスの作成2018

    • Author(s)
      江頭良明, 森靖典, 柳川右千夫, 高森茂雄.
    • Organizer
      第41回日本神経科学大会
    • Related Report
      2018 Research-status Report
  • [Presentation] Endosomal Q-SNARE Syntaxin-7 specifies a subpopulation of recycling synaptic vesicles preferentially responsive to high frequency stimulation.2018

    • Author(s)
      Mori Y, Takenaka K, Fukazawa Y, Takamori S.
    • Organizer
      JSPS Core-to-Core Symposium “Nanobiology of neural plasticity based on optical nanoscopy”
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Expression of plasma membrane calcium ATPases confers Ca2+/H+ exchange in rodent synaptic vesicles.2018

    • Author(s)
      Ono Y, Sumiyama K, Mori Y, Egashira Y, Takamori S.
    • Organizer
      JSPS Core-to-Core Symposium “Nanobiology of neural plasticity based on optical nanoscopy”
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Remarks] 髙森茂雄研究室(オリジナルサイト)

    • URL

      https://takamorilab.wixsite.com/takamori-lab

    • Related Report
      2020 Annual Research Report
  • [Remarks]

    • URL

      https://brainscience.doshisha.ac.jp/

    • Related Report
      2018 Research-status Report
  • [Remarks]

    • URL

      https://takamorilab.wixsite.com/takamori-lab

    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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