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Clarification of the reciprocal interactions between Amot and Lats in activation of the Hippo pathway

Research Project

Project/Area Number 25440112
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Developmental biology
Research InstitutionTokyo Medical and Dental University (2014-2015)
Kumamoto University (2013)

Principal Investigator

Hirate Yoshikazu  東京医科歯科大学, 実験動物センター, 講師 (70342839)

Co-Investigator(Renkei-kenkyūsha) SASAKI HIROSHI  大阪大学, 大学院生命機能研究科, 教授 (10211939)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Keywords発生・分化 / シグナル伝達 / 細胞間コミュニケーション / Hippo経路 / 細胞極性 / 非対称分裂 / Angiomotin / Lats
Outline of Final Research Achievements

The Hippo signaling pathway regulates a number of cellular events, including the control of cell fates in preimplantation mouse embryos. The inner and outer cells of the embryo show high and low levels of Hippo signaling, respectively. This position-dependent Hippo signaling promotes the specification of distinct cell fates. The junction-associated scaffold protein Angiomotin (Amot) plays a key role in this mechanism. At the adherens junctions of the inner cells, Amot activates the Hippo pathway by recruiting and activating the protein kinase large tumor suppressor (Lats). In contrast, Amot at the apical membrane of the outer cells suppresses Hippo signaling by interacting with F-actin. The phosphorylation of Amot inhibits its interaction with F-actin and activates Hippo signaling. We propose that Amot acts as a molecular switch for the Hippo pathway and links F-actin with Lats activity.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2015 2014 2013 Other

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

  • [Journal Article] Par-aPKC-dependent and -independent mechanisms cooperatively control cell polarity, Hippo signaling, and cell positioning in 16-cell stage mouse embryos2015

    • Author(s)
      Hirate, Y., Hirahara, S., Inoue, K., Kiyonari, H., Niwa, H., and Sasaki, H.
    • Journal Title

      Development, Growth and Differentiation

      Volume: 57 Issue: 8 Pages: 544-556

    • DOI

      10.1111/dgd.12235

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The role of angiomotin phosphorylation in the Hippo pathway during preimplantation mouse development2014

    • Author(s)
      Hirate Y. and Sasaki H.
    • Journal Title

      Tissue Barriers

      Volume: 2

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Polarity-dependent distribution of angiomotin localizes Hippo signaling in preimplantation embryos.2013

    • Author(s)
      Hirate Y, Hirahara S, Inoue K-i, Suzuki A, Alarcon VB, Akimoto K, Hirai T, Hara T, Adachi M, Chida K, Ohno S, Marikawa Y, Nakao K, Shimono A, Sasaki H
    • Journal Title

      Curr. Biol.

      Volume: 23 Issue: 13 Pages: 1181-1194

    • DOI

      10.1016/j.cub.2013.05.014

    • Related Report
      2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] マウス着床前胚の細胞分化制御におけるHippo経路と細胞極性の役割2015

    • Author(s)
      平手 良和
    • Organizer
      第108回日本繁殖生物学会大会
    • Place of Presentation
      宮崎市民プラザ(宮崎県・宮崎市)
    • Year and Date
      2015-09-17
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス着床前胚の細胞分化はAngiomotinリン酸化によるHippo経路の活性化によって制御されている2014

    • Author(s)
      平手良和、平原志乃、井上健一、鈴木厚、Vernadeth B. Alarcon、秋本和憲、平井孝明、千田和広、大野茂男、Yusuke Marikawa、中尾和貴、下野明彦、佐々木洋
    • Organizer
      第61回日本実験動物学会総会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2014-05-15 – 2014-05-17
    • Related Report
      2014 Research-status Report
  • [Presentation] Phosphorylation of Angiomotin regulates the Hippo pathway in cell fate regulation of preimplantation mouse embryos2014

    • Author(s)
      平手良和、平原志乃、井上健一、鈴木厚、Vernadeth B. Alarcon、秋本和憲、平井孝明、千田和広、大野茂男、Yusuke Marikawa、中尾和貴、下野明彦、佐々木洋
    • Organizer
      第61回日本実験動物学会総会
    • Place of Presentation
      札幌コンベンションセンター
    • Related Report
      2013 Research-status Report
  • [Remarks] 熊本大学発生医学研究所分化制御分野

    • URL

      http://www.imeg.kumamoto-u.ac.jp/divisions/cell_fate_control/index.html

    • Related Report
      2014 Research-status Report
  • [Remarks] トピックス

    • URL

      http://www.imeg.kumamoto-u.ac.jp/topics/sasaki130626.html

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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