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A feedback mechanism between the plasma membrane and the actin cytoskeleton underneath during cell migration

Research Project

Project/Area Number 19K06638
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionKobe University

Principal Investigator

Itoh Toshiki  神戸大学, バイオシグナル総合研究センター, 教授 (30313092)

Project Period (FY) 2019-04-01 – 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 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords細胞運動 / 細胞膜 / 細胞骨格 / Rac / F-BARドメイン / 膜張力 / アクチン細胞骨格 / がん / F-BAR / actin / cell motility
Outline of Research at the Start

運動する細胞において「広がった細胞膜が退縮すること」は重要であり、伸展した細胞膜の形状や張力を感知してRacをオフにするフィードバック制御の存在が示唆される。F-BARドメインをもつFBP17は細胞膜張力の低下を感知しアクチン重合を活性化するが、逆反応である「膜の広がりに伴う張力の上昇を感知してアクチン重合を抑制するメカニズム」は不明である。本研究では、伸展した細胞膜の先端に局在するsrGAPに着目する。膜先端にかかる張力とそれに伴う高度な膜の凹面を感知するメカニズムを明らかにし、srGAPが伸展した細胞膜の先端でアクチン重合のネガティブフィードバック因子として機能することを実証する。

Outline of Final Research Achievements

In cell migration, the cytoskeleton exerts a driving force by stretching the plasma membrane by pushing it from the inside. A feedback mechanism that regulates the retraction of the extended plasma membrane is vital for efficient cell movement, but its molecular detail is unknown. In this study, we focused on a group of proteins that control and sense the tension applied to the plasma membrane with the activity of regulating the actin cytoskeleton. Our results reveal a part of the feedback mechanism between the plasma membrane and the actin cytoskeleton underneath during cell migration.

Academic Significance and Societal Importance of the Research Achievements

細胞運動は個体発生や免疫機能などの生理的なプロセスにおいてだけでなく、がん悪性化などの重篤な病態に関わる重要な生命現象である。複雑な組織組織内を移動していくため、運動する細胞は自身の形態を柔軟に変化させ、その進路を効率的に選択する必要がある。本研究の成果は、このダイナミックな現象を支えるメカニズムの一端を明らかにするものであり、細胞運動が関わる生理、病理現象の理解への新たな理解と、これまでにない介入アプローチが期待される。

Report

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

    (15 results)

All 2022 2021 2019 Other

All Journal Article (7 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 7 results,  Open Access: 4 results) Presentation (6 results) Remarks (1 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Homeostatic membrane tension constrains cancer cell dissemination by counteracting BAR protein assembly2021

    • Author(s)
      Tsujita Kazuya、Satow Reiko、Asada Shinobu、Nakamura Yoshikazu、Arnes Luis、Sako Keisuke、Fujita Yasuyuki、Fukami Kiyoko、Itoh Toshiki
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 5930-5930

    • DOI

      10.1038/s41467-021-26156-4

    • NAID

      120007165701

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] FBP17-mediated finger-like membrane protrusions in cell competition between normal and RasV12-transformed cells2021

    • Author(s)
      Kamasaki Tomoko、Miyazaki Yumi、Ishikawa Susumu、Hoshiba Kazuya、Kuromiya Keisuke、Tanimura Nobuyuki、Mori Yusuke、Tsutsumi Motosuke、Nemoto Tomomi、Uehara Ryota、Suetsugu Shiro、Itoh Toshiki、Fujita Yasuyuki
    • Journal Title

      iScience

      Volume: 24 Issue: 9 Pages: 102994-102994

    • DOI

      10.1016/j.isci.2021.102994

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Physical Properties and Reactivity of Microdomains in Phosphatidylinositol-Containing Supported Lipid Bilayer2021

    • Author(s)
      Toshinori Motegi, Kingo Takiguchi, Yohko Tanaka-Takiguchi, Toshiki Itoh, Ryugo Tero
    • Journal Title

      Membranes

      Volume: 11 Issue: 5 Pages: 339-339

    • DOI

      10.3390/membranes11050339

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PTEN is required for the migration and invasion of Ras‐transformed MDCK cells2021

    • Author(s)
      Yan Lu、Tsujita Kazuya、Fujita Yasuyuki、Itoh Toshiki
    • Journal Title

      FEBS Letters

      Volume: - Issue: 9 Pages: 1303-1312

    • DOI

      10.1002/1873-3468.14053

    • Related Report
      2021 Annual Research Report 2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Non-cell-autonomous migration of RasV12-transformed cells towards the basal side of surrounding normal cells2021

    • Author(s)
      Jebri Imen、Tsujita Kazuya、Fujita Yasuyuki、Itoh Toshiki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 543 Pages: 15-22

    • DOI

      10.1016/j.bbrc.2021.01.031

    • NAID

      120006996928

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] SH3YL1 cooperates with ESCRT-I in the sorting and degradation of the EGF receptor2019

    • Author(s)
      Hasegawa Junya、Jebri Imen、Yamamoto Hikaru、Tsujita Kazuya、Tokuda Emi、Shibata Hideki、Maki Masatoshi、Itoh Toshiki
    • Journal Title

      Journal of Cell Science

      Volume: 132 Issue: 19 Pages: 229179-229179

    • DOI

      10.1242/jcs.229179

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] An influenza-derived membrane tension-modulating peptide regulates cell movement and morphology via actin remodeling2019

    • Author(s)
      Masuda Toshihiro、Baba Kentarou、Nomura Takeshi、Tsujita Kazuya、Murayama Tomo、Itoh Toshiki、Takatani-Nakase Tomoka、Sokabe Masahiro、Inagaki Naoyuki、Futaki Shiroh
    • Journal Title

      Communications Biology

      Volume: 2 Issue: 1 Pages: 243-243

    • DOI

      10.1038/s42003-019-0486-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] DA-Rafは細胞膜と活性化Rasに結合することによりRas-ERK経路の全体的抑制因子として機能する2021

    • Author(s)
      高野和儀 , 辻田和也 , 伊藤俊樹 , 遠藤剛
    • Organizer
      日本生化学会大会(Web)
    • Related Report
      2021 Annual Research Report
  • [Presentation] 膜曲率誘導タンパク質による細胞膜張力の制御機構2021

    • Author(s)
      辻田和也 , 伊藤俊樹
    • Organizer
      日本細胞生物学会大会(Web)
    • Related Report
      2021 Annual Research Report
  • [Presentation] Vitamin E induces palmitoylation of 67kDa laminin receptor by direct binding .2021

    • Author(s)
      岡本聖香, 林大輝, 足立直子, Varnavas Mouchlis, 上田修司, 山之上稔, Edward Dennis, 伊藤俊樹, 斎藤 尚亮, 白井康仁
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Research-status Report
  • [Presentation] The Dynamic Changes in PI(4,5)P2 and PI(3,4,5)P3 are Required for the Elimination of RasG12V Transformed Cells by Cell Competition2019

    • Author(s)
      閻 露、伊藤俊樹
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] リン脂質結合タンパク質SH3YL1の機能解析2019

    • Author(s)
      伊藤俊樹、山本 光、ジェブリイメン
    • Organizer
      第60回日本組織細胞化学会総会・学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] メカノバイオロジー研究の新展開 ―"力"による生命現象制御の理解深化に向けて―2019

    • Author(s)
      辻田和也、伊藤俊樹
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Remarks] 神戸大学バイオシグナル総合研究センター 伊藤研究室

    • URL

      http://www.research.kobe-u.ac.jp/brce-itoh/papers.html

    • Related Report
      2019 Research-status Report
  • [Patent(Industrial Property Rights)] CANCER THERAPY2022

    • Inventor(s)
      辻田和也、伊藤俊樹、深見希代子、佐藤礼子
    • Industrial Property Rights Holder
      辻田和也、伊藤俊樹、深見希代子、佐藤礼子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2022
    • Related Report
      2021 Annual Research Report
    • Overseas

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

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