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Regulatory meachnism of protein phosphatase 2A on smooth muscle mechano-chmical coupling

Research Project

Project/Area Number 16K08500
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionTokyo Metropolitan University

Principal Investigator

WATANABE MASARU  首都大学東京, 人間健康科学研究科, 教授 (60191798)

Co-Investigator(Kenkyū-buntansha) 竹谷 浩介  岡山理科大学, 獣医学部, 講師 (20586862)
Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords平滑筋 / プロテインホスファターゼ / ミオシン軽鎖リン酸化 / アクチン ミオシン相互作用 / プロテインホスファターゼ2A / 収縮 / ミオシン / アクチン / フィラメント構造 / Caイオン感受性 / 収縮タンパク質 / プロテインホスファターゼ2A / スキンド標本 / ラッチ / x線回折 / ミオシンアクチン相互作用 / ラッチ機構
Outline of Final Research Achievements

To clarify the mechanisms of the PP2A effects on the smooth muscle contractile proteins in vivo, we studied the effects of rubratoxin A, a specific PP2A inhibitor, on contraction of beta escin skinned (cell membrane permeabilized) taenia cecum from guinea pig. Rubratoxin A, irreversibly inhibited Ca ion induced contraction of skinned preparations with suppression of myosin light cahin (MLC) phosphorylation at 100 - 1000 nM. Also,the agent seems to inhibit MLC kinase activity. Similar concentrations of the agent also seemed to slightly inhibit pharmacological concentrations Mg ion induced, MLC-phosphorylation independent, contraction, an experimental model of "Latch" formation.These results suggest that PP2A causes up-regulation of the MLC and direct interference with myosin-actin interaction.

Academic Significance and Societal Importance of the Research Achievements

本研究は、従来、平滑筋研究において専ら焦点があてられてきたrP(プロテインホスファターゼ)1に比べて情報量が圧倒的に少なかったPP2Aが、平滑筋収縮機構を活性化させることを世界に先駆けて解明した。特に、平滑筋収縮の主調整機構であるミオシン軽鎖リン酸化機構と、収縮反応の最下流であるミオシンーアクチン結合機構の双方を調節することから、PP2Aが平滑筋収縮のアクチベーターとして機能すると結論される。
従って、PP2A活性の人為的調節より血管攣縮等の平滑筋異常収縮を効果的に阻害できる可能性が示唆される。本研究の発展により新たな平滑筋異常収縮への治療戦略を構築したい。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (8 results)

All 2020 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (5 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Accelerating effects of blebbistatin on relaxation process of cell membrane permeabilized trachea and taenia cecum from guinea pig2020

    • Author(s)
      Mihashi S, Ishida Y, Watanabe M.
    • Journal Title

      Journal of Smooth Muscle Research

      Volume: 56 Issue: 0 Pages: 19-28

    • DOI

      10.1540/jsmr.56.19

    • NAID

      130007836996

    • ISSN
      0916-8737, 1884-8796
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibitory effects of rubratoxin A, a potent inhibitor of protein phosphatase 2, on the Ca<sup>2+</sup>-dependent contraction of skinned carotid artery from guinea pig2019

    • Author(s)
      Yasuyuki NARAKI, Masaru WATANABE, Kousuke TAKEYA
    • Journal Title

      Journal of Smooth Muscle Research

      Volume: 55 Issue: 0 Pages: 14-22

    • DOI

      10.1540/jsmr.55.14

    • NAID

      130007634980

    • ISSN
      0916-8737, 1884-8796
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Protein phosphatases 1 and 2A and their naturally occurring inhibitors: current topics in smooth muscle physiology and chemical biology2018

    • Author(s)
      Takai A, Eto M, Hirano K, Takaya K, Wakimoto T, Watanabe M
    • Journal Title

      The Jounral of Physiological Sciences

      Volume: 68 Issue: 2 Pages: 1-17

    • DOI

      10.1007/s12576-017-0577-1

    • NAID

      40021443577

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Natural products induced disruption of actin polymerization modulate mechanical responses of skinned smooth muscle through various pathways.2020

    • Author(s)
      Watanabe M.
    • Organizer
      第97回日本生理学会大会(誌上開催)
    • Related Report
      2019 Annual Research Report
  • [Presentation] Regulation of thick and thin filaments organization of smooth muscle contraction2019

    • Author(s)
      Masaru WATANABE, Naoya NAKAHARA, Yukisato Ishida
    • Organizer
      FAOPS2019
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 選択的プロテインホスファターゼ2A阻害薬rubratoxinAはβエスシンスキンド平滑筋収縮の潜時を延長する2018

    • Author(s)
      楢木 康之, 渡辺 賢
    • Organizer
      第60回日本平滑筋学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Mechanisms of inhibitory effects of protein phosphatase 2A on smooth muscle contraction2017

    • Author(s)
      Masaru Watanabe, Kousuke Takeya
    • Organizer
      第94回日本生理学会大会
    • Place of Presentation
      アクトシティ浜松(浜松市)
    • Year and Date
      2017-03-30
    • Related Report
      2016 Research-status Report
  • [Presentation] Rubratoxin A, a specific protein phosphatase 2A inhibitor, suppresses smooth muscle contraction through myosin light chain phosphorylation dependent and independent pathways2017

    • Author(s)
      Watanabe M, Naraki Y, Takeya K
    • Organizer
      The 3rd Japan-Taiwan Protein Phspatase Symposium
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research

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Published: 2016-04-21   Modified: 2021-02-19  

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