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Mechanically activated protein kinases regulate mesenchymal-epithelial transition-like reaction in early embryonic ectoderm

Research Project

Project/Area Number 20K06663
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44020:Developmental biology-related
Research InstitutionNational Institute for Basic Biology

Principal Investigator

Kinoshita Noriyuki  基礎生物学研究所, 初期発生研究部門, 准教授 (30300940)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Keywordsアフリカツメガエル胚 / 力学刺激 / 細胞接着 / ERK / マウス / 子宮 / 上皮細胞 / プロテインキナーゼ / 初期胚 / 密着結合 / ZO-1 / タンパク質リン酸化 / タイトジャンクション / アフリカツメガエル / 初期発生 / 力学応答 / プロテイン・キナーゼ
Outline of Research at the Start

動物の胚発生の過程では、組織の運動によって物理的な力が生まれている。私たちはアフリカツメガエル胚に力学刺激を与えることで、様々なタンパク質のリン酸化状態が変化し、細胞接着や細胞骨格が大きく変化することを見出した。本研究は、そのような変化を引き起こすメカニズムについて、プロテイン・キナーゼを中心に、その活性制御機構、下流の基質タンパク質などの解析を通して力学応答のシグナル伝達機構を明らかにし、発生におけるその意義・役割を解明する。

Outline of Final Research Achievements

During the morphogenesis process in animal embryo development, various movements such as tissue movement, extension, contraction, and bending occur. These movements generate physical forces. In this study, I used Xenopus embryos and mouse embryos and uterine tissues to analyze how cells sense mechanical stimuli and trigger responses, focusing on protein kinases. As a result, I found that in both Xenopus and mouse, mechanical stimuli activate ERK, and that a receptor tyrosine kinase exists upstream of ERK. I also found that the role of ERK in the mechanical response is important in controlling the localization of the tight junction protein ZO-1 in epithelial cells.

Academic Significance and Societal Importance of the Research Achievements

細胞の力学応答の仕組みの研究はまだ始まったばかりであり、多くの謎が残された研究分野である。本研究は、アフリカツメガエル胚に機械刺激を与え、その変化をリン酸化プロテオミクスにより解析するという独自の系を端に発し、その知見から、力学刺激に応じたプロテインキナーゼ活性化による細胞接着制御を明らかにした点が新しく、学術的意義のある点であると考える。力学刺激は、たとえば力学負荷による骨の増強など、医学分野への関わりも明らかになりつつあり、社会的にも意義深いと考えている。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2024 2023 2022 2021 2020 Other

All Journal Article (4 results) (of which Peer Reviewed: 2 results,  Open Access: 3 results) Presentation (2 results) Remarks (2 results)

  • [Journal Article] Tight junction membrane proteins regulate the mechanical resistance of the apical junctional complex2024

    • Author(s)
      Nguyen Thanh Phuong、Otani Tetsuhisa、Tsutsumi Motosuke、Kinoshita Noriyuki、Fujiwara Sachiko、Nemoto Tomomi、Fujimori Toshihiko、Furuse Mikio
    • Journal Title

      Journal of Cell Biology

      Volume: 223 Issue: 5 Pages: 1-23

    • DOI

      10.1083/jcb.202307104

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanical transapical coupling of endometrial epithelial cells during implantation2023

    • Author(s)
      Sakurai Jun、Kinoshita Noriyuki、Otani Tetsuhisa、Koyama Hiroshi、Furuse Mikio、Fujimori Toshihiko
    • Journal Title

      BioRxiv

      Volume: - Pages: 571398-571398

    • DOI

      10.1101/2023.12.12.571398

    • Related Report
      2023 Annual Research Report
    • Open Access
  • [Journal Article] Force-dependent remodeling of cytoplasmic ZO-1 condensates contributes to cell-cell adhesion through enhancing tight junctions2022

    • Author(s)
      Kinoshita, Noriyuki Yamamoto, Takamasa S. Yasue, Naoko Takagi, Chiyo Fujimori, Toshihiko Ueno, Naoto
    • Journal Title

      iScience

      Volume: 25 Issue: 2 Pages: 103846-103846

    • DOI

      10.1016/j.isci.2022.103846

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Force-dependent remodeling of a tight junction protein ZO-1 is regulated by phase separation2020

    • Author(s)
      Kinoshita Noriyuki、Yamamoto Takamasa S.、Yasue Naoko、Fujimori Toshihiko、Ueno Naoto
    • Journal Title

      bioRxiv

      Volume: -

    • DOI

      10.1101/2020.10.04.323436

    • Related Report
      2020 Research-status Report
    • Open Access
  • [Presentation] Regulation of collective cell migration via ZO-1 phase separation2022

    • Author(s)
      HIRANO Sayuki, KINOSHITA Noriyuki, AOKI Kazuhiro , UENO Naoto
    • Organizer
      日本発生生物学会
    • Related Report
      2022 Research-status Report
  • [Presentation] Force-dependent remodeling of a tight junction protein ZO-1 is regulated by phase separation2021

    • Author(s)
      Noriyuki Kinoshita, Takamasa Yamamoto, Naoko Yasue, Chiyo Takagi, Toshihiko Fujimori, and Naoto Ueno
    • Organizer
      日本発生生物学会
    • Related Report
      2021 Research-status Report
  • [Remarks] 引き伸ばされても細胞同士がバラバラにならないわけ ~力学的ストレスに耐える新たな仕組みを解明~

    • URL

      https://www.nibb.ac.jp/pressroom/news/2024/03/22.html

    • Related Report
      2023 Annual Research Report
  • [Remarks] 細胞間接着の新たな制御機構の発見

    • URL

      https://www.nibb.ac.jp/press/2022/02/25.html

    • Related Report
      2021 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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