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Identification of secreted proteins in neuromuscular junction

Research Project

Project/Area Number 18K06483
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 InstitutionNagoya University

Principal Investigator

Ohkawara Bisei  名古屋大学, 医学系研究科, 准教授 (80589606)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords神経筋接合部 / 運動神経細胞 / 筋肉細胞 / シナプス形成 / 細胞外分泌因子 / 細胞外マトリックス
Outline of Final Research Achievements

Neuromuscular junctions (NMJ) is a synapse between spinal motor neuron and skeletal muscle. Whole factors and those mechanism, which are involved in NMJ formation and maturation, remain elusive. In this project, in order to identify excellular secretory factors for NMJ formation and maturation, I have focused on mRNA and proteins, which are expressed in the NMJ during embryonic stages, and performed with muscle cell line, C2C12 myotubes. As a result, it was found that the extracellular secretory factors, Agrin and CTGF, have a roles in the NMJ morphogenesis with those characteristic domains, respectively. In addition, several factors and drugs that function together them were identified in the project.

Academic Significance and Societal Importance of the Research Achievements

NMJで機能する細胞外分泌因子の全用途そのメカニズムを知ることで、神経シナプス形成における細胞外分泌因子の役割を知るための基盤となる知識が得られる。アセチルコリン受容体などNMJで機能する分子の先天的な遺伝子変異によってもたらされる先天性筋無力症候群の病態研究にもつながる。

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 2022 2021 2020

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (1 results) (of which Invited: 1 results)

  • [Journal Article] Meclozine ameliorates skeletal muscle pathology and increases muscle forces in mdx mice2022

    • Author(s)
      Kawamura Yusuke、Hida Tetsuro、Ohkawara Bisei、Matsushita Masaki、Kobayashi Takeshi、Ishizuka Shinya、Hiraiwa Hideki、Tanaka Satoshi、Tsushima Mikito、Nakashima Hiroaki、Ito Kenyu、Imagama Shiro、Ito Mikako、Masuda Akio、Ishiguro Naoki、Ohno Kinji
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 592 Pages: 87-92

    • DOI

      10.1016/j.bbrc.2022.01.003

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulated splicing of large exons is linked to phase‐separation of vertebrate transcription factors2021

    • Author(s)
      Kawachi Toshihiko、Masuda Akio、Yamashita Yoshihiro、Takeda Jun‐ichi、Ohkawara Bisei、Ito Mikako、Ohno Kinji
    • Journal Title

      The EMBO Journal

      Volume: 40 Issue: 22

    • DOI

      10.15252/embj.2020107485

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zonisamide upregulates neuregulin-1 expression and enhances acetylcholine receptor clustering at the in vitro neuromuscular junction2021

    • Author(s)
      Inoue Taro、Ohkawara Bisei、Bushra Samira、Kanbara Shunsuke、Nakashima Hiroaki、Koshimizu Hiroyuki、Tomita Hiroyuki、Ito Mikako、Masuda Akio、Ishiguro Naoki、Imagama Shiro、Ohno Kinji
    • Journal Title

      Neuropharmacology

      Volume: 195 Pages: 108637-108637

    • DOI

      10.1016/j.neuropharm.2021.108637

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Secreted Signaling Molecules at the Neuromuscular Junction in Physiology and Pathology2021

    • Author(s)
      Ohkawara Bisei、Ito Mikako、Ohno Kinji
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 5 Pages: 2455-2455

    • DOI

      10.3390/ijms22052455

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Congenital myasthenic syndrome?associated agrin variants affect clustering of acetylcholine receptors in a domain-specific manner2020

    • Author(s)
      Ohkawara Bisei、Shen XinMing、Selcen Duygu、Nazim Mohammad、Bril Vera、Tarnopolsky Mark A.、Brady Lauren、Fukami Sae、Amato Anthony A.、Yis Uluc、Ohno Kinji、Engel Andrew G.
    • Journal Title

      JCI Insight

      Volume: 5 Issue: 7

    • DOI

      10.1172/jci.insight.132023

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] CTGF/CCN2 facilitates LRP4‐mediated formation of the embryonic neuromuscular junction2020

    • Author(s)
      Ohkawara Bisei、Kobayakawa Akinori、Kanbara Shunsuke、Hattori Takako、Kubota Satoshi、Ito Mikako、Masuda Akio、Takigawa Masaharu、Lyons Karen M、Ishiguro Naoki、Ohno Kinji
    • Journal Title

      EMBO reports

      Volume: 21 Issue: 8

    • DOI

      10.15252/embr.201948462

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Zonisamide ameliorates progression of cervical spondylotic myelopathy in a rat model2020

    • Author(s)
      Kanbara Shunsuke、Ohkawara Bisei、Nakashima Hiroaki、Ohta Kyotaro、Koshimizu Hiroyuki、Inoue Taro、Tomita Hiroyuki、Ito Mikako、Masuda Akio、Ishiguro Naoki、Imagama Shiro、Ohno Kinji
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 13138-13138

    • DOI

      10.1038/s41598-020-70068-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Zonisamide ameliorates neuropathic pain partly by suppressing microglial activation in the spinal cord in a mouse model2020

    • Author(s)
      Koshimizu Hiroyuki、Ohkawara Bisei、Nakashima Hiroaki、Ota Kyotaro、Kanbara Shunsuke、Inoue Taro、Tomita Hiroyuki、Sayo Akira、Kiryu-Seo Sumiko、Konishi Hiroyuki、Ito Mikako、Masuda Akio、Ishiguro Naoki、Imagama Shiro、Kiyama Hiroshi、Ohno Kinji
    • Journal Title

      Life Sciences

      Volume: 263 Pages: 118577-118577

    • DOI

      10.1016/j.lfs.2020.118577

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gene Expression Profile at the Motor Endplate of the Neuromuscular Junction of Fast-Twitch Muscle2020

    • Author(s)
      Huang Kun、Li Jin、Ito Mikako、Takeda Jun-Ichi、Ohkawara Bisei、Ogi Tomoo、Masuda Akio、Ohno Kinji
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 13 Pages: 154-154

    • DOI

      10.3389/fnmol.2020.00154

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] tRIP-seq Reveals Repression of Premature Polyadenylation by Co-Transcriptional FUS-U1 snRNP Assembly2020

    • Author(s)
      Akio Masuda, Toshihiko Kawachi, Jun-Ichi Takeda, Bisei Ohkawara, Mikako Ito, Kinji Ohno
    • Journal Title

      EMBO Rep.

      Volume: - Issue: 5

    • DOI

      10.15252/embr.201949890

    • NAID

      120006884959

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 神経筋接合部形成における細胞外分泌因子の役割2020

    • Author(s)
      大河原美静
    • Organizer
      第6回日本筋学会学術集会
    • Related Report
      2020 Research-status Report
    • Invited

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

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