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The mechanism of osmo-regulatory signal transduction by interactions among membrane proteins through their TM regions

Research Project

Project/Area Number 24247034
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionThe University of Tokyo

Principal Investigator

SAITO Haruo  東京大学, 医科学研究所, 教授 (60114485)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥45,890,000 (Direct Cost: ¥35,300,000、Indirect Cost: ¥10,590,000)
Fiscal Year 2014: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
Fiscal Year 2013: ¥14,560,000 (Direct Cost: ¥11,200,000、Indirect Cost: ¥3,360,000)
Fiscal Year 2012: ¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
KeywordsSignal transduction / Yeast / Osmoregulation / Membrane protein / MAP kinase / シグナル伝達 / 酵母 / 浸透圧応答 / 膜タンパク質 / MAPキナーゼ / 4回膜タンパク質
Outline of Final Research Achievements

When exposed to hyperosmolarity, the budding yeast Saccharomyces cerevisiae activates the Hog1 MAP kinase signal pathway, which governs an array of adaptive responses. In this project, we investigated how the activity of the Hog1 MAPK pathway is regulated by the Sho1 osmosensor and the Hkr1/Msb2 co-osmosensors. First, we determined the oligomeric structure of the 4TM osmosensor Sho1 using a site-directed chemical crosslinking strategy. External osmolarity influenced the internal structure of the Sho1 oligomer as well as the interactions between the Sho1 oligomers and cytoplasmic signaling proteins. Second, we found that specific and dynamic bindings of the Hkr1/Msb2 co-osmosensors to the membrane anchorage protein Opy2 and to cytoplasmic scaffold proteins are essential for Hog1 activation. From these results, details of the mechanism of Hog1 activation by external high osmolarity are revealed.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (10 results)

All 2015 2014 2013 2012 Other

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (2 results) (of which Invited: 2 results) Remarks (2 results)

  • [Journal Article] MCRIP1, an ERK substrate, mediates ERK-induced epigenetic gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP2015

    • Author(s)
      Kenji Ichikawa, Yuji Kubota, Takanori Nakamura, Jane S. Weng, Taichiro Tomida, Haruo Saito and Mutsuhiro Takekawa
    • Journal Title

      Molecular Cell

      Volume: 58 Issue: 1 Pages: 35-46

    • DOI

      10.1016/j.molcel.2015.01.023

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Osmosensing and scaffolding functions of the oligomeric four-transmembrane domain osmosensor Sho1.2015

    • Author(s)
      Tatebayashi K, Yamamoto K, Nagoya M, Takayama T, Nishimura A, Sakurai M, Momma T, and Saito H.
    • Journal Title

      Nature Communications

      Volume: 6 Issue: 1 Pages: 6975-6975

    • DOI

      10.1038/ncomms7975

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Yeast osmosensors Hkr1 and Msb2 activate the Hog1 MAPK cascade by different mechanisms2014

    • Author(s)
      K. Tanaka, K. Tatebayashi, A. Nishimura, K. Yamamoto, H.Y. Yang, and H. Saito
    • Journal Title

      Science Signaling

      Volume: 7 Issue: 314 Pages: 1-10

    • DOI

      10.1126/scisignal.2004780

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress.2013

    • Author(s)
      Nakamura, T.
    • Journal Title

      Nature Commun.

      Volume: 4 Issue: 1 Pages: 1775-1775

    • DOI

      10.1038/ncomms2752

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The temporal pattern of stimulation determines the extent and duration of MAPK activation in a Caenorhabditis elegans sensory neuron2012

    • Author(s)
      Tomida, T., Oda, S., Takekawa, M., Iino, Y., and Saito, H
    • Journal Title

      Sci Signal

      Volume: 5 Issue: 246 Pages: 76-76

    • DOI

      10.1126/scisignal.2002983

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Response to hyperosmotic stress2012

    • Author(s)
      H. Saito and F. Posas
    • Journal Title

      Genetics

      Volume: 192 Issue: 2 Pages: 289-318

    • DOI

      10.1534/genetics.112.140863

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Dynamic regulation of hyperosmotic stress signaling in the budding yeast

    • Author(s)
      H. Saito
    • Organizer
      第22回 国際生化学・分子生物学会議
    • Place of Presentation
      スペイン セビリア
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Role of membrane proteins in osmoregulatory signal transduction in yeast

    • Author(s)
      H. Saito
    • Organizer
      PRBB会議
    • Place of Presentation
      スペイン バルセロナ
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Remarks] 東京大学医科学研究所 分子細胞情報分野 斎藤研究室ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/MolCellSignal/index.html

    • Related Report
      2013 Annual Research Report
  • [Remarks] 東京大学医科学研究所 分子細胞情報分野 ホームページ

    • URL

      http://www.ims.u-tokyo.ac.jp/MolCellSignal/index.html

    • Related Report
      2012 Annual Research Report

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Published: 2013-05-15   Modified: 2019-07-29  

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