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Analysis of the importance and mechanisms of the nuclear positioning in mature neurons

Research Project

Project/Area Number 19K22476
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 46:Neuroscience and related fields
Research InstitutionShimane University

Principal Investigator

Kuwako Ken-ichiro  島根大学, 学術研究院医学・看護学系, 准教授 (30468475)

Project Period (FY) 2019-06-28 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2019: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords神経突起 / 核 / ニューロン / 局在 / 生理機能
Outline of Research at the Start

成熟神経細胞では、一般的に核は細胞の中央に位置しているが、その位置がどのようなメカニズムで決定され、どのような機能的意味をもつのかはわかっていない。そこで、本研究では、成熟マウス小脳神経細胞をモデルとして、核の位置制御の分子機構を解明する。そして、その機構の破綻によって引き起こされる神経機能の異常を明らかにし、成熟神経細胞の“核の位置”の重要性に迫る。

Outline of Final Research Achievements

The nuclear membrane LINC complex is known as important molecules regulating nuclear positioning. To clarify the unknown functions of the LINC complex, in this study, we performed functional inhibition experiments in cultured neurons and mouse brains. We found that the LINC complex was essential for the formation and maintenance of the axon initial segment, that is the site of action potential generation, in developing and mature neurons. This study suggests the existence of a new regulatory system of neuronal activity via the nucleus.

Academic Significance and Societal Importance of the Research Achievements

これまで核を起点とした神経突起や神経活動の制御システムはほとんど知られておらず、またLINC複合体はほぼ全ての神経細胞で発現していることから、本研究は多様な脳神経機能の基盤をなす重要かつ普遍的な機構の存在を明らかにしたと考えられる。今後、本研究で発見した機構が脳の発生や疾患、老化などの幅広い現象に関与する可能性を明らかにしていくことで脳機能の基本作動原理の理解が深まると期待される。

Report

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

    (10 results)

All 2022 2021 2020 2019

All Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 2 results) Presentation (6 results) (of which Invited: 1 results)

  • [Journal Article] Molecular mechanisms regulating the spatial configuration of neurites.2022

    • Author(s)
      Hasegawa K and Kuwako K
    • Journal Title

      Seminars in Cell and Developmental Biology

      Volume: - Pages: 103-114

    • DOI

      10.1016/j.semcdb.2022.02.015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Vascularization of human brain organoids2021

    • Author(s)
      Matsui TK, Tsuru Y, Hasegawa K, Kuwako KI
    • Journal Title

      Stem Cells

      Volume: 0 Issue: 8 Pages: 0-0

    • DOI

      10.1002/stem.3368

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The polymicrogyria-associated GPR56 promoter preferentially drives gene expression in developing GABAergic neurons in common marmosets2020

    • Author(s)
      Murayama AY, Kuwako KI, Okahara J, Bae BI, Okuno M, Mashiko H, Shimogori T, Walsh CA, Sasaki E, Okano H
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 21516-21516

    • DOI

      10.1038/s41598-020-78608-4

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Challenges in Modeling Human Neural Circuit Formation via Brain Organoid Technology2020

    • Author(s)
      Matsui TK, Tsuru Y, Kuwako KI
    • Journal Title

      Frontiers in Cellular Neuroscience

      Volume: 14 Pages: 607399-607399

    • DOI

      10.3389/fncel.2020.607399

    • NAID

      120007002189

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] LINC complex regulates the plasticity of axon initial segment2022

    • Author(s)
      Hasegawa K. Matsui TK, Kondo J, Shoji S, Hama N, Kuwako K
    • Organizer
      日本生理学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Analysis of the synaptic connections in the developing preBotzinger complex2021

    • Author(s)
      Hama N, Kato T, Yokota S, Hasegawa K, Kuwako K
    • Organizer
      日本神経科学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Analysis of the nucleoskeletal and cytoskeletal-anchoring protein Nesprin-1 on the axon initial segment for neuronal polarity and plasticity2021

    • Author(s)
      Hasegawa K. Matsui TK, Kondo J, Ishihara T, Kuwako K
    • Organizer
      日本神経科学会
    • Related Report
      2021 Annual Research Report
  • [Presentation] i-GONAD法によるチロシナーゼ遺伝子ヒマラヤ変異マウスの作製2021

    • Author(s)
      雪澤瞳、長谷川孝一、桑子 賢一郎
    • Organizer
      西日本医学生学術フォーラム2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] ヒト脊髄オルガノイドの作成2021

    • Author(s)
      都留佑一朗、松井健、長谷川孝一、桑子 賢一郎
    • Organizer
      西日本医学生学術フォーラム2021
    • Related Report
      2021 Annual Research Report
  • [Presentation] 脳神経回路をつくる発生システム2019

    • Author(s)
      桑子賢一郎
    • Organizer
      奈良県立医科大学特別セミナー
    • Related Report
      2019 Research-status Report
    • Invited

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Published: 2019-07-04   Modified: 2023-01-30  

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