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Roles of the signal transduction via lipid rafts in axon formation and regeneration

Research Project

Project/Area Number 18K06480
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 InstitutionNiigata University

Principal Investigator

HONDA ATSUKO  新潟大学, 医歯学系, 特任助教 (40467072)

Co-Investigator(Kenkyū-buntansha) 伊藤 泰行  新潟大学, 医歯学系, 助教 (70710573)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords脂質ラフト / 神経軸索伸長 / 成長円錐 / 神経発生 / 神経軸索再生 / M6a / シグナル伝達 / 神経極性 / 神経成長円錐 / M6aタンパク質 / シグナル伝達分子 / プロテオミクス / リピドミクス / 小胞体 / 極長鎖脂肪酸産生酵素 / 神経軸索形成 / EMARS標識法 / 軸索形成 / 軸索再生 / 神経損傷 / EMARS標識 / lipid raft / axon regeneration / axon formation / EMARS / signal transduction
Outline of Final Research Achievements

To clarify regulatory mechanisms of the signals for axon formation, we examined the activation system of the signal transduction through the lipid rafts by a membrane protein, M6a in the neuronal growth cones (GC). We analyzed the molecules interacting with M6a on plasma membrane, or the proteins localized in GC lipid rafts via M6a, using proteomic analysis. Our proteomic data showed that M6a interacts with adhesion molecules, e.g. Integrin, the receptors and endoplasmic reticulum on plasma membrane, and recruits some determinants of the neuronal polarity, some kinases, G-proteins and some lipid synthases to lipid rafts. These data indicated that the extra-intra cellular signal transductions and the lipid synthesis in the lipid rafts were intensified by M6a in the GC.

Academic Significance and Societal Importance of the Research Achievements

神経軸索形成機構の解明は、発生期の脳形成過程や,成体の神経損傷後の再生過程を理解する上で不可欠である。本研究成果は、成長過程の軸索先端部分である成長円錐において軸索形成を制御する分子群が、どのように「脂質ラフト」とよばれる膜の微小領域(マイクロドメイン)で会合して活性化されるのか、その実体を示すものであり、脂質ラフトの生理的意義を実証するとともに、M6a発現の関与する精神疾患や脳症などの病態解明とその治療法、神経損傷後の軸索再生治療への応用など、臨床医学への発展が強く期待される。

Report

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

    (11 results)

All 2020 2019

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (8 results) (of which Int'l Joint Research: 8 results)

  • [Journal Article] Phosphoproteomic and Bioinformatic Methods for Analyzing Signaling in Vertebrate Axon Growth and Regeneration2020

    • Author(s)
      Igarashi M, Kawasaki A, Ishikawa Y, Honda A, Okada M, Okuda S.
    • Journal Title

      Journal of Neuroscience Methods

      Volume: 339 Pages: 108723-108723

    • DOI

      10.1016/j.jneumeth.2020.108723

    • Related Report
      2020 Annual Research Report 2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neuronal Signaling Involved in Neuronal Polarization and Growth: Lipid Rafts and Phosphorylation2020

    • Author(s)
      Igarashi Michihiro、Honda Atsuko、Kawasaki Asami、Nozumi Motohiro
    • Journal Title

      Frontiers in Molecular Neuroscience

      Volume: 13 Pages: 1-11

    • DOI

      10.3389/fnmol.2020.00150

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylation sites of microtubule-associated protein 1B (MAP1B) involved in axon growth and regeneration2019

    • Author(s)
      Ishikawa Y, Okada M, Honda A, Ito Y, Tamada A, Endo N, Igarashi M
    • Journal Title

      Molecular Brain

      Volume: 12 Issue: 1 Pages: 31711525-31711525

    • DOI

      10.1186/s13041-019-0510-z

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Physiological functions of GPSN2, an enzyme synthesizing VLCFA in the neuronal development.2020

    • Author(s)
      Atsuko Honda, Motohiro Nozumi, Haruki Uchino, Makoto Arita, and Michihiro Igarashi
    • Organizer
      第43回 日本神経科学大会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経発生過程における極長鎖脂肪酸産生酵素GPSN2の生理的役割2020

    • Author(s)
      本多 敦子, 野住 素広, 内野 春希, 有田 誠, 五十嵐 道弘
    • Organizer
      第93回 日本生化学会大会
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 神経軸索成長・再生過程に特異的なMAP1Bのリン酸化2019

    • Author(s)
      本多敦子、石川裕也、五十嵐道弘
    • Organizer
      第92回 日本生化学大会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Lipoquality and development of the GPSN2 knockout mice2019

    • Author(s)
      Michihiro Igarashi, Atsuko Honda, Motohiro Nozumi
    • Organizer
      60th International Conference on the Bioscience of Lipids
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 発生脳におけるMAP1Bの高頻度リン酸化部位2019

    • Author(s)
      石川裕也、本多敦子、伊藤泰行、河嵜麻実、玉田篤史、遠藤直人、五十嵐道弘
    • Organizer
      第42回日本神経科学・第62回日本神経化学合同大会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] The MAP1B phosphorylation sites specifically localized in the developing brain and in the regenerating peripheral nerves2019

    • Author(s)
      石川裕也、岡田正康、本多敦子、伊藤泰行、玉田篤史、遠藤直人、五十嵐道弘
    • Organizer
      SFN annual Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脳発生過程で高頻度にリン酸化されるMAP1Bチロシン残基の同定と機能解析2019

    • Author(s)
      伊藤泰行、本多敦子、五十嵐道弘
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 高頻度チロシンリン酸化MAP1Bの神経発生過程における機能解析2019

    • Author(s)
      伊藤泰行、本多敦子、五十嵐道弘
    • Organizer
      第42回日本神経科学・第62回日本神経化学合同大会
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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

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