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Nuclear membrane maintenance by nuclear membrane protein Lem2 and Lnp1

Research Project

Project/Area Number 19K23725
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0701:Biology at molecular to cellular levels, and related fields
Research InstitutionHiroshima University

Principal Investigator

Kinugasa Yasuha  広島大学, 原爆放射線医科学研究所, 助教 (60852118)

Project Period (FY) 2019-08-30 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
KeywordsLem2 / Lnp1 / ESCRT-III / 核膜 / 小胞体膜 / 脂質 / 生細胞イメージング / CLEM / ESCRTIII / イメージング / クロマチン
Outline of Research at the Start

核膜タンパク質はクロマチン機能を高度に制御することで、細胞活動に伴うダイナミックな遺伝子発現変動を可能としている。しかし、核膜タンパク質は機能重複が多く解析が困難なことから、制御機構の全容は未だ明らかになっていない。本研究課題では核膜タンパク質Lem2とLnp1がクロマチンだけでなく核膜構造にも影響することに着目し、Lem2・Lnp1が核膜構造を制御する分子メカニズムを遺伝学・細胞生物学・生化学的手法を用いて解析することで、核膜タンパク質による核膜構造を介したクロマチン制御機構を明らかにする。

Outline of Final Research Achievements

This study focuses on the nuclear envelope proteins Lem2 and Lnp1 and aims to elucidate the mechanism by which the nuclear envelope proteins regulate the morphology and function of the nuclear membrane. Analysis using live cell imaging and correlative light-electron microscopy (CLEM) revealed that Lem2 and Lnp1 maintain the boundary between the nuclear membrane and the endoplasmic reticulum membrane. Furthermore, by analysis with components of membrane repairing complex ESCRT-III, it was clarified that Lem2 and Lnp1 correctly localize Vps4 on the membrane and maintain membrane remodeling, which leads to the maintenance of the nuclear membrane.

Academic Significance and Societal Importance of the Research Achievements

核膜の機能維持は真核細胞の生存にとって最も重要な要因の一つであり、そのメカニズムの解明は学術的に重要な課題である。また、核膜タンパク質の変異は、筋ジストロフィー、早老症といった様々な重篤疾患を引き起こすことが知られており、核膜タンパク質の機能解明は社会的にも重要である。解析が容易な分裂酵母で得られた成果は、ヒトをはじめとする真核生物に普遍的な仕組みの理解に繋がるため、今後多様な分野へ応用することが出来る可能性を有している。

Report

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

    (8 results)

All 2020 2019

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

  • [Journal Article] Lem2 and Lnp1 maintain the membrane boundary between the nuclear envelope and endoplasmic reticulum2020

    • Author(s)
      Hirano Yasuhiro、Kinugasa Yasuha、Osakada Hiroko、Shindo Tomoko、Kubota Yoshino、Shibata Shinsuke、Haraguchi Tokuko、Hiraoka Yasushi
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 276-276

    • DOI

      10.1038/s42003-020-0999-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Roles of Remote and Contact Forces in Epithelial Cell Structure Formation2020

    • Author(s)
      Nakano Tadashi、Okaie Yutaka、Kinugasa Yasuha、Koujin Takako、Suda Tatsuya、Hiraoka Yasushi、Haraguchi Tokuko
    • Journal Title

      Biophysical Journal

      Volume: 118 Issue: 6 Pages: 1466-1478

    • DOI

      10.1016/j.bpj.2020.01.037

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Evaluating Individual Radiosensitivity for the Prediction of Acute Toxicities of Chemoradiotherapy in Esophageal Cancer Patients2020

    • Author(s)
      Imano Nobuki、Nishibuchi Ikuno、Kawabata Emi、Kinugasa Yasuha、Shi Lin、Sakai Chiemi、Ishida Mari、Sakane Hiroaki、Akita Tomoyuki、Ishida Takafumi、Kimura Tomoki、Murakami Yuji、Tanaka Kimio、Horikoshi Yasunori、Sun Jiying、Nagata Yasushi、Tashiro Satoshi
    • Journal Title

      Radiation Research

      Volume: 195 Issue: 3 Pages: 244-252

    • DOI

      10.1667/rade-20-00234.1

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The very-long-chain fatty acid elongase Elo2 rescues lethal defects associated with loss of the nuclear barrier function in fission yeast cells2019

    • Author(s)
      Kinugasa Yasuha、Hirano Yasuhiro、Sawai Megumi、Ohno Yusuke、Shindo Tomoko、Asakawa Haruhiko、Chikashige Yuji、Shibata Shinsuke、Kihara Akio、Haraguchi Tokuko、Hiraoka Yasushi
    • Journal Title

      Journal of Cell Science

      Volume: 132 Issue: 10 Pages: 229021-229021

    • DOI

      10.1242/jcs.229021

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Lem2による核膜形態維持機構とゲノム安定化における役割2019

    • Author(s)
      平野泰弘、衣笠泰葉、原口徳子、平岡泰
    • Organizer
      第37回染色体ワークショップ・第18回細胞核ダイナミクス研究会
    • Related Report
      2019 Research-status Report
  • [Presentation] Lem2と Lnp1は Vps4-ESCRT-III複合体の機能を制御することで核膜-小胞体構造を維持する2019

    • Author(s)
      平野泰弘、衣笠泰葉、原口徳子、平岡泰
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Lem2 and Lnp1 cooperatively maintain the nuclear membrane integrity through ESCRT-III functions2019

    • Author(s)
      Hirano Y, Kinugasa Y, Osakada H, Shindo T, Kubota Y, Shibata S, Haraguchi T, Hiraoka Y
    • Organizer
      The International Fission Yeast Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Very-long-chain fatty acid elongase Elo2 rescues chromosomal defects associated with loss of nuclear membrane protein Lem22019

    • Author(s)
      Kinugasa Y, Hirano Y, Asakawa H, Chikashige Y, Haraguchi T, Hiraoka Y
    • Organizer
      The International Fission Yeast Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research

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Published: 2019-09-03   Modified: 2022-01-27  

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