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Roles of Golgi apparatus dynamics regulated by Reelin signaling in neuronal homeostasis

Research Project

Project/Area Number 18K06543
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 46030:Function of nervous system-related
Research InstitutionInstitute for Developmental Research Aichi Developmental Disability Center

Principal Investigator

Matsuki Tohru  愛知県医療療育総合センター発達障害研究所, 細胞病態研究部, 主任研究員 (90332329)

Co-Investigator(Kenkyū-buntansha) 中山 敦雄  愛知県医療療育総合センター発達障害研究所, 細胞病態研究部, 部長 (50227964)
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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsSTK25 / Rac1 / RhoA / 神経細動移動 / 大脳皮質形成 / genetic compensation / MST3 / Reelin / ゴルジ体 / GM130 / PKC / 神経細胞移動 / Rho-GTPase / Reelinシグナル / ゴルジ体構造制御 / ゴルジ小胞 / 記憶・学習 / Stk25シグナル
Outline of Final Research Achievements

During cortical lamination, neuronal migration is precisely regulated and critical for functional brain development. Here we resolve the conundrum that although the acute disruption of Stk25 causes a defect in neuronal migration, constitutive Stk25-null mice have no histological aberrations. MST3, a member of the GCKIII subgroup of the Ste20-like kinase family, compensates for STK25 by playing similar roles in several biological functions. In vivo, MST3 overexpression in Stk25-knockout neurons rescued neuronal migration and axonogenesis. Mechanistically, we find that STK25 acts through the Cul3/Bacurd1 complex to activate Rac1 and degrade of RhoA, through in vivo rescue experiments. Collectively, our findings demonstrate that STK25 and MST3 have redundant roles to regulate Rho GTPases and provide a detailed link between STK25 and regulation of the actin cytoskeleton.

Academic Significance and Societal Importance of the Research Achievements

大脳皮質形成時においてRho-GTPaseファミリーが重要な役割を果たしている事はこれまでに明らかにされていたが、STK25がRac1とRhoAの機能調節両方に関与する事を初めて示す事が出来た。また、今回の研究成果ではgenetic compensationについても言及しており、その代償機構の一端を明らかにする事が出来た。本成果は、genetic compensationが働いていると考えられる他の分子を研究上で重要な視点を与えるとともに、大脳皮質形成機構の解明を前進させる事に貢献できたと確信している。

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

    (11 results)

All 2021 2020 2019 2018 Other

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

  • [Int'l Joint Research] SUNY Upstate Medical University(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] SUNY Upstate Medical University(米国)

    • Related Report
      2020 Research-status Report
  • [Int'l Joint Research] Brian W. Howell/SUNY Upstate Medical University(米国)

    • Related Report
      2019 Research-status Report
  • [Int'l Joint Research] State University of New York(米国)

    • Related Report
      2018 Research-status Report
  • [Journal Article] STK25 and MST3 Have Overlapping Roles to Regulate Rho GTPases during Cortical Development2021

    • Author(s)
      Matsuki Tohru、Iio Akio、Ueda Masashi、Tsuneura Yumi、Howell Brian W.、Nakayama Atsuo
    • Journal Title

      The Journal of Neuroscience

      Volume: 41 Issue: 43 Pages: 8887-8903

    • DOI

      10.1523/jneurosci.0523-21.2021

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The α1-adrenergic receptors in the amygdala regulate the induction of learned despair through protein kinase C-beta signaling2021

    • Author(s)
      Shisui Fujita, Satomi Yoshida, Tohru Matsuki, Manoj Kumar Jaiswal and Kenjiro Seki
    • Journal Title

      Behavioural Pharmacology

      Volume: 32 Issue: 1 Pages: 73-85

    • DOI

      10.1097/fbp.0000000000000605

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Knockdown of Son, a Mouse Homologue of the ZTTK Syndrome Gene, Causes Neuronal Migration Defects and Dendritic Spine Abnormalities2020

    • Author(s)
      Masashi Ueda, Tohru Matsuki, Masahide Fukada, Shima Eda, Akie Toya, Akio Iio, Hidenori Tabata, Atsuo Nakayama
    • Journal Title

      Molecular Brain

      Volume: 13 Issue: 1 Pages: 80-80

    • DOI

      10.1186/s13041-020-00622-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] STK25が関与する大脳皮質形成機構2021

    • Author(s)
      松木亨、飯尾明生、上田昌史、常浦裕未、中山敦雄
    • Organizer
      第53回日本臨床分子形態学会総会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Stk25 acts as a hub protein for the Rho-GTPases regulation in an MST3 compensation manner during cortical development2019

    • Author(s)
      松木亨
    • Organizer
      日本神経科学会第42回大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Stk25 and MST3 act on neuronal polarization and migration in a compensation manner.2018

    • Author(s)
      松木亨、飯尾明生、上田昌史、戸谷明恵、中山敦雄
    • Organizer
      日本神経科学学会
    • Related Report
      2018 Research-status Report
  • [Book] 細胞培養実習テキスト  第2版2020

    • Author(s)
      日本組織培養学会編
    • Total Pages
      161
    • Publisher
      じほう
    • ISBN
      9784840752923
    • Related Report
      2020 Research-status Report

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

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