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Molecular mechanisms of neurite self-avoidance

Research Project

Project/Area Number 18K06207
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionThe University of Tokyo

Principal Investigator

Kise Yoshiaki  東京大学, 大学院理学系研究科(理学部), 特任准教授 (70769611)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords樹状突起 / 軸索 / イオンチャネル / 自己交叉忌避 / シグナル伝達
Outline of Final Research Achievements

This project aims to reveal the molecular mechanisms of neuronal development, maintenance, and function in the brain. To this end, we first identified the regulators of cytoskeleton which work downstream of cell-recognition molecule Dscam for dendrite self-avoidance. Second, we identified Wnk kinase which is required for the growth/branching as well as maintenance of axon. Finally, we provided, by using cryo-EM, the structural basis for gating modulation of Kv4.2-KChIP1-DPP6S channel complex which is required for the inhibition of the backpropagation of the action potential in dendrites.

Academic Significance and Societal Importance of the Research Achievements

我々ヒトの脳神経系は、1000億個もの神経細胞がその複雑な分枝パターンをもった樹状突起と軸索を介して精密なネットワークを形成し、情報処理、運動、学習、意思決定などを行う。本研究成果の学術的な意義は、(1)樹状突起や軸索の分枝パターン形成と維持の機構を明らかしたこと、(2)神経細胞が機能的電気信号を生み出すために必須なカリウムチャネルの活性制御機構を明らかにしたことによって、神経細胞の発生と機能の両面のメカニズムに迫ることができた点である。その社会的意義は、損傷を受けた脳の再生や、イオンチャネルの機能不全による精神疾患の治療という医療への応用にも道を切り開いたことである。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (13 results)

All 2021 2019 Other

All Int'l Joint Research (5 results) Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] ボン大学(ドイツ)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Bonn University(ドイツ)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] University of Leuven(ベルギー)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] University of Leuven(ベルギー)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] Iowa State University(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] Axon morphogenesis and maintenance require an evolutionary conserved safeguard function of Wnk kinases antagonizing Sarm and Axed2021

    • Author(s)
      Izadifar A, Courchet J, Virga DM, Verreet T, Hamilton S, Ayaz D, Misbaer A, Vandenbogaerde S, Monteiro L, Petrovic M, Sachse S, Yan B, Erfurth ML, Dascenco D, Kise Y, Yan J, Edwards-Faret G, Lewis T, Polleux F, Schmucker D.
    • Journal Title

      Neuron

      Volume: 109 Issue: 18 Pages: 2864-2883

    • DOI

      10.1016/j.neuron.2021.07.006

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structural basis of gating modulation of Kv4 channel complexes.2021

    • Author(s)
      Kise Y, Kasuya G, Okamoto HH, Yamanouchi D, Kobayashi K, Kusakizako T, Nishizawa T, Nakajo K, Nureki O.
    • Journal Title

      Nature

      Volume: 599 Issue: 7883 Pages: 158-164

    • DOI

      10.1038/s41586-021-03935-z

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Nuclear import of the DSCAM-cytoplasmic domain drives signaling capable of inhibiting synapse formation.2019

    • Author(s)
      Sachse SM, Lievens S, Ribeiro LF, Dascenco D, Masschaele D, Horre K, Misbaer A, Vanderroost N, De Smet AS, Salta E, Erfurth ML, Kise Y, Nebel S, Van Delm W, Plaisance S, Tavernier J, De Strooper B, De Wit J, Schmucker D.
    • Journal Title

      EMBO J

      Volume: 38 Issue: 6

    • DOI

      10.15252/embj.201899669

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Structural basis of gating modulation of the Kv4 macromolecular channel complex2021

    • Author(s)
      Yoshiaki Kise
    • Organizer
      生理研研究会「構造情報を基盤とした膜機能分子の生理機能理解に向けて」
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Wnk regulates Nmnat and Axundead during axon morphogenesis and maintenance2019

    • Author(s)
      Izadifar A., Courchet J., Verreet T., Ayaz D., Petrovic M., Sachse S. Misbaer A., Vandenbogaerde S., Yan B., Erfurth ML, Dascenco D., Kise Y., Yan J., Lewis T., Polleux F., Schmucker D.
    • Organizer
      3rd Axon Meeting "Circuits Development & Axon Regeneration" at Spain
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Molecular signaling pathways regulating axon branching via Dscam12019

    • Author(s)
      Kise Y, Izadifar A, Schmucker D, Emoto K
    • Organizer
      The 41st Annual Meeting of the Japan Neuroscience Society in 2018 at Kobe
    • Related Report
      2018 Research-status Report
  • [Remarks] 制御サブユニットによるイオンチャネル巨大複合体のモジュレーション機構を解明

    • URL

      https://www.s.u-tokyo.ac.jp/ja/press/2021/7525/

    • Related Report
      2021 Annual Research Report
  • [Remarks]

    • URL

      http://www.s.u-tokyo.ac.jp/en/press/2021/7569/

    • Related Report
      2021 Annual Research Report

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Published: 2018-04-23   Modified: 2023-01-30  

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