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Molecular Mechanisms for the formation of periodic cytoskeletal structures in axons

Research Project

Project/Area Number 17K07118
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionOsaka University

Principal Investigator

YOSHIMURA Takeshi  大阪大学, 連合小児発達学研究科, 講師 (60402567)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords神経細胞 / 軸索 / 細胞骨格 / Spectrin / リン酸化
Outline of Final Research Achievements

Axons have a specific cytoskeletal structure lining the cytoplasmic face of the axolemma. Super-resolution microscopy has revealed a remarkable periodic lattice in axons. αII-spectrin is the only α spectrin detected in the nervous system, and forms the periodic lattice in axons. While αII-spectrin intracellular localization is fairly well understood, the molecular mechanism by which αII-spectrin was regulated remains unclear. In this study, we report that Cdk5 phosphorylates αII-spectrin. We identified the phosphorylation site of αII-spectrin by Cdk5, and made anti-phospho-specific αII-spectrin antibody. The phosphorylated αII-spectrin was localized in the axon initial segment. Inhibition of Cdk5 impaired axon initial segment formation and neuronal polarity. These results suggest that Cdk5 regulates the axonal periodic cytoskeleton through the phosphorylation of αII-spectrin.

Academic Significance and Societal Importance of the Research Achievements

本研究により、神経細胞においてCdk5はαII-spectrinのリン酸化を介して軸索特異的な細胞骨格構造の形成に重要な役割を果たすことが明らかとなった。本研究により軸索に特異的な細胞骨格の形成機構が分かることで、情報出力を担う軸索の基盤の理解が深まると考えられる。ウエスト症候群は既知の小児難治てんかんの中では最も多い、精神運動発達の退行を伴う指定難病である。この疾患に関わるαII-spectrinの制御機構の解明はその病因解明の糸口になると期待される。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (20 results)

All 2021 2020 2019 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (12 results) (of which Int'l Joint Research: 2 results) Remarks (3 results)

  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2018 Research-status Report
  • [Int'l Joint Research] ベイラー医科大学(米国)

    • Related Report
      2017 Research-status Report
  • [Journal Article] A perspective on the role of dynamic alternative RNA splicing in the development, specification, and function of axon initial segment.2019

    • Author(s)
      Iijima Takatoshi, Yoshimura Takeshi
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 12 Pages: 295-295

    • DOI

      10.3389/fnmol.2019.00295

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Cdk5はαII-spectrinのリン酸化を介して軸索に特異的な細胞骨格構造を制御する2021

    • Author(s)
      吉村 武, ラズバンド マシュー, 片山 泰一
    • Organizer
      第126回日本解剖学会総会・全国学術集会 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Cdk5はαII-spectrinのリン酸化を介して軸索の周期的細胞骨格構造を制御する2020

    • Author(s)
      吉村 武, Rasband Matthew, 片山 泰一
    • Organizer
      第63回日本神経化学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 精神・神経疾患に関わる軸索起始部の構造形成の分子機構2020

    • Author(s)
      吉村 武, Matthew N Rasband, 片山 泰一
    • Organizer
      第125回日本解剖学会総会・全国学術集会(山口県宇部市)(誌上開催)
    • Related Report
      2019 Research-status Report
  • [Presentation] Cdk5 regulates phosphorylation of ankyrin-G and axon initial segment formation.2019

    • Author(s)
      Takeshi Yoshimura, Matthew N. Rasband, Taiichi Katayama
    • Organizer
      NEURO2019(第42回 日本神経科学大会・第62回 日本神経化学会大会)(新潟県新潟市)
    • Related Report
      2019 Research-status Report
  • [Presentation] Phosphorylation of cytoskeletal proteins in axon initial segments2019

    • Author(s)
      Takeshi Yoshimura, Matthew Rasband, Taiichi Katayama
    • Organizer
      the 2019 ISN-ASN Meeting(国際神経化学会大会)(Montreal, Canada)
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 精神・神経疾患を惹起する軸索起始部の構造破綻の分子機構2019

    • Author(s)
      吉村 武, Matthew N Rasband, 片山 泰一
    • Organizer
      第46回日本脳科学学会(滋賀県大津市)
    • Related Report
      2019 Research-status Report
  • [Presentation] Cdk5はAnkyrin Gのリン酸化を介して軸索起始部の形成を制御する2019

    • Author(s)
      吉村 武, Matthew Rasband, 片山 泰一
    • Organizer
      第124回日本解剖学会総会・全国学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] 精神・神経疾患に関わる神経軸索の膜裏打ち構造の形成機構の解明2018

    • Author(s)
      吉村武
    • Organizer
      第4回 包括的神経グリア研究会
    • Related Report
      2017 Research-status Report
  • [Presentation] Axon initial segment cytoskeleton shows a more complicated pattern during brain development.2017

    • Author(s)
      Takeshi Yoshimura, Sharon R. Stevens, Cristophe Leterrier, Michael C. Stankewich, Genki Amano, Sarina Han, Sho Shikada, Hironori Takamura, Ko Miyoshi, Matthew N. Rasband, Taiichi Katayama
    • Organizer
      第60回 日本神経化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 神経軸索に特異的な膜直下細胞骨格の形成機構2017

    • Author(s)
      吉村武, 片山泰一
    • Organizer
      第18回 ORIGIN 神経科学研究会 2017
    • Related Report
      2017 Research-status Report
  • [Presentation] Axon initial segment cytoskeleton shows a more complicated pattern during brain development.2017

    • Author(s)
      Takeshi Yoshimura, Sharon R. Stevens, Cristophe Leterrier, Michael C. Stankewich, Genki Amano, Sarina Han, Sho Shikada, Hironori Takamura, Ko Miyoshi, Matthew N. Rasband, Taiichi Katayama
    • Organizer
      ISN-ESN 2007 Meeting
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 軸索基始部とランビエ絞輪の細胞骨格は脳発達に伴い複雑になる2017

    • Author(s)
      吉村武
    • Organizer
      平成29年度研究会「神経科学の新しい解析法とその応用」「グリア細胞機能から迫る脳機能解明」
    • Related Report
      2017 Research-status Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.ugscd.osaka-u.ac.jp/mbs/index.html

    • Related Report
      2020 Annual Research Report
  • [Remarks] http://www.ugscd.osaka-u.ac.jp/mbs/index.html

    • Related Report
      2019 Research-status Report
  • [Remarks] ホームページ

    • URL

      http://www.ugscd.osaka-u.ac.jp/mbs/index.html

    • Related Report
      2018 Research-status Report 2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-02-21  

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