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Mechanism of regulation of liquid-liquid phase separation by importin-beta

Research Project

Project/Area Number 19K16060
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43020:Structural biochemistry-related
Research InstitutionRitsumeikan University

Principal Investigator

Yoshizawa Takuya  立命館大学, 生命科学部, 講師 (50779056)

Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords液-液相分離 / 核内輸送受容体 / RNA結合タンパク質 / 筋萎縮性側索硬化症 / 液-液相分離 / インポーチンβファミリー / インポーチン
Outline of Research at the Start

液-液相分離は、ストレス顆粒などの膜の無いオルガネラを説明できる現象として、近年大きな注目を集めている。その優位性は、周囲の環境に応じて形成と消失を行える柔軟性にある。本研究では、ストレス顆粒のもととなる液‐液相分離を抑制(ほどく)因子のインポーチンβファミリーに着目して研究を行う。インポーチンβがどのような相互作用を介して液-液相分離を抑制するか、分子レベルで明らかにすることを目指す。

Outline of Final Research Achievements

Nuclear import receptors, karyopherin-βs inhibit liquid-liquid phase separation (LLPS) of client proteins. Dysregulation of LLPS leads to an aggregation of the client proteins, eventually causing fatal neurodegenerative diseases including amyotrophic lateral sclerosis (ALS). We studied dysregulation by mutations of the client protein or repeat peptide inhibitor bound to karyopherin-βs. In addition, we developed a new technique to track forming or vanishing droplets by LLPS.

Academic Significance and Societal Importance of the Research Achievements

液-液相分離を調節するタンパク質の解析は未だ事例が少なく、新たなシャペロンのカテゴリーとして開拓されつつある領域であり、そのメカニズムに迫った(学術的意義)。また、液-液相分離相分離の状態は解析が困難であり、新規な解析法を開発した(学術的意義)。タンパク質の凝集は重篤な疾患とも密接に関わり、疾患関連変異体や関連遺伝子産物を用いた本研究は、病態の発症メカニズムに迫るものである(社会的意義)。

Report

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

    (18 results)

All 2022 2021 2020 2019 Other

All Journal Article (10 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 5 results) Presentation (7 results) (of which Invited: 4 results) Remarks (1 results)

  • [Journal Article] Pressure and Temperature Phase Diagram for Liquid-Liquid Phase Separation of the RNA-Binding Protein Fused in Sarcoma2021

    • Author(s)
      Li Shujie、Yoshizawa Takuya、Yamazaki Ryota、Fujiwara Ayano、Kameda Tomoshi、Kitahara Ryo
    • Journal Title

      The Journal of Physical Chemistry B

      Volume: 125 Issue: 25 Pages: 6821-6829

    • DOI

      10.1021/acs.jpcb.1c01451

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Karyopherin-βs play a key role as a phase separation regulator2021

    • Author(s)
      Yoshizawa Takuya、Guo Lin
    • Journal Title

      The Journal of Biochemistry

      Volume: 170 Issue: 1 Pages: 15-23

    • DOI

      10.1093/jb/mvab072

    • NAID

      40022722268

    • Related Report
      2021 Annual Research Report
  • [Journal Article] C9orf72-derived arginine-rich poly-dipeptides impede phase modifiers2021

    • Author(s)
      Nanaura Hitoki、Aiba Yuichiro、Nakanishi Mari、Shiota Tomo、Hibino Masaki、Kikuchi Sotaro、Nagata Riko、Morikawa Naritaka、Iguchi Naohiko、Kiriyama Takao、Nagamori Shushi、Sugie Kazuma、Saio Tomohide、Yoshizawa Takuya、Mori Eiichiro et al.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 5301-5301

    • DOI

      10.1038/s41467-021-25560-0

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Pressure-Jump Kinetics of Liquid-Liquid Phase Separation: Comparison of Two Different Condensed Phases of the RNA-Binding Protein, Fused in Sarcoma2021

    • Author(s)
      Kitahara Ryo、Yamazaki Ryota、Ide Fumika、Li Shujie、Shiramasa Yutaro、Sasahara Naoya、Yoshizawa Takuya
    • Journal Title

      Journal of the American Chemical Society

      Volume: 143 Issue: 47 Pages: 19697-19702

    • DOI

      10.1021/jacs.1c07571

    • Related Report
      2021 Annual Research Report
  • [Journal Article] Mechanism of karyopherin-β2 binding and nuclear import of ALS variants FUS(P525L) and FUS(R495X)2021

    • Author(s)
      Gonzalez Abner、Mannen Taro、Cagatay Tolga、Fujiwara Ayano、Matsumura Hiroyoshi、Niesman Ashley B.、Brautigam Chad A.、Chook Yuh Min、Yoshizawa Takuya
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 3754-3754

    • DOI

      10.1038/s41598-021-83196-y

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effect of nuclear import receptors on liquid–liquid phase separation2020

    • Author(s)
      Yoshizawa Takuya、Matsumura Hiroyoshi
    • Journal Title

      Biophysics and Physicobiology

      Volume: 17 Issue: 0 Pages: 25-29

    • DOI

      10.2142/biophysico.BSJ-2019052

    • NAID

      130007828794

    • ISSN
      2189-4779
    • Year and Date
      2020-04-04
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Crystal structures of the cell-division protein FtsZ from Klebsiella pneumoniae and Escherichia coli2020

    • Author(s)
      Yoshizawa Takuya、Fujita Junso、Terakado Haruna、Ozawa Mayuki、Kuroda Natsuko、Tanaka Shun-ichi、Uehara Ryo、Matsumura Hiroyoshi
    • Journal Title

      Acta Crystallographica Section F Structural Biology Communications

      Volume: 76 Issue: 2 Pages: 86-93

    • DOI

      10.1107/s2053230x2000076x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Biological phase separation: cell biology meets biophysics2020

    • Author(s)
      Takuya Yoshizawa、Ryu-Suke Nozawa、Tony Z. Jia、Tomohide Saio、Eiichiro Mori
    • Journal Title

      Biophysical Reviews

      Volume: 12 Issue: 2 Pages: 519-539

    • DOI

      10.1007/s12551-020-00680-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] COX6A2 variants cause a muscle-specific cytochrome c oxidase deficiency2019

    • Author(s)
      Inoue Michio、Uchino Shumpei、Iida Aritoshi、Noguchi Satoru、Hayashi Shinichiro、Takahashi Tsutomu、Fujii Katsunori、Komaki Hirofumi、Takeshita Eri、Nonaka Ikuya、Okada Yukinori、Yoshizawa Takuya、Van Lommel Leentje、Schuit Frans、Goto Yu‐ichi、Mimaki Masakazu、Nishino Ichizo
    • Journal Title

      Annals of Neurology

      Volume: 86 Issue: 2 Pages: 193

    • DOI

      10.1002/ana.25517

    • URL

      https://localhost/en/publications/d3fc9351-ad37-4e0c-904e-2872575d6ac2

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Structure-Guided Design of a Fluorescent Probe for the Visualization of FtsZ in Clinically Important Gram-Positive and Gram-Negative Bacterial Pathogens2019

    • Author(s)
      Ferrer-Gonzalez Edgar、Fujita Junso、Yoshizawa Takuya、Nelson Julia M.、Pilch Alyssa J.、Hillman Elani、Ozawa Mayuki、Kuroda Natsuko、Al-Tameemi Hassan M.、Boyd Jeffrey M.、LaVoie Edmond J.、Matsumura Hiroyoshi、Pilch Daniel S.
    • Journal Title

      Scientific Reports

      Volume: 9 Issue: 1 Pages: 20092-20092

    • DOI

      10.1038/s41598-019-56557-x

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] 相分離するRNA結合タンパク質と相分離を制御する核輸送タンパク質2022

    • Author(s)
      吉澤 拓也、藤原 綾乃、上原 武尊、井手 郁佳、笹原 直哉、松村 浩由
    • Organizer
      日本化学会 第102春季年会 (2022)
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] アルギニンリッチ配列と相分離制御2021

    • Author(s)
      吉澤拓也
    • Organizer
      第21回日本蛋白質科学会年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] RNA結合タンパク質の相分離制御に関する研究2021

    • Author(s)
      吉澤拓也
    • Organizer
      日本結晶学会2021年度年会
    • Related Report
      2021 Annual Research Report
    • Invited
  • [Presentation] Molecular basis of Karyopherin-β2 binding and nuclear import of ALS-related FUS2020

    • Author(s)
      Takuya Yoshizawa, Taro Mannen, Ayano Fujiwara, Hiroyoshi Matsumura
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] ほどける相分離:シャペロンとしてはたらく核輸送タンパク質2019

    • Author(s)
      吉澤拓也
    • Organizer
      第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会合同年次大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Nuclear import receptor blocks liquid-liquid phase separation of RNA binding protein2019

    • Author(s)
      Takuya Yoshizawa
    • Organizer
      第19回日本蛋白質科学会年会・第71回日本細胞生物学会大会合同年次大会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] FUSの液-液相分離とImportinβファミリー2019

    • Author(s)
      吉澤拓也
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Remarks] 研究ハイライト : 相分離がつなぐ生命現象と今後の展望

    • Related Report
      2019 Research-status Report

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Published: 2019-04-18   Modified: 2023-01-30  

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