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Genome-wide screen-based identification of non-selective hypertonicity-induced cation channel

Research Project

Project/Area Number 17K15086
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Watanabe Kengo  東京大学, 大学院薬学系研究科(薬学部), 特任助教 (20781727)

Research Collaborator MORISHITA Kazuhiro  
Project Period (FY) 2017-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords高浸透圧ストレス / HICC / ゲノムワイドsiRNAスクリーニング / ASK3 / ストレス / シグナル伝達
Outline of Final Research Achievements

Similar to slugs poured salt on, cells shrink when the concentration of extracellular solution becomes higher than that of intracellular solution, which is called as hyperosmotic stress. If this goes on, cells die; therefore, cells recover their volume to survive. To achieve cell volume recovery, cells firstly have to recognize the state under hyperosmotic stress. It is said that the protein passing ions, called HICC, is the cellular sensor for hyperosmotic stress; however, the molecular identity of HICC remains unclear. In this study, the scientist investigated about 20,000 proteins coded on the human genome one by one to identify the components of HICC. Although he could not surely identify it during this period, he successfully obtained the candidate protein and important knowledge establishing a foothold to further researches.

Academic Significance and Societal Importance of the Research Achievements

液体と接している細胞は常に浸透圧ストレスに晒されるリスクがあり,浸透圧ストレスに適切に応答する仕組みは細胞が生存する上で必須の基本的なシステムの1つである.さらに細胞はこのシステムを浸透圧ストレスに対抗する時だけでなく,分裂や移動する時など体積を変化させる細胞機能時にも利用すると言われている.つまり,このシステムの異常が高血圧やがん,炎症などの疾患に関わっている可能性がある.本研究はシステムを始動させるセンサー部分に着目したものであり,本成果を足掛かりにシステムの全貌解明に向けてさらに研究を発展させることで,様々な疾患に対する創薬基盤・治療戦略の開発に資することが期待される.

Report

(3 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017 Other

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

  • [Journal Article] Cryo-EM structures of the human volume-regulated anion channel LRRC82018

    • Author(s)
      Kasuya G, Nakane T, Yokoyama T, Jia Y, Inoue M, Watanabe K, Nakamura R, Nishizawa T, Kusakizako T, Tsutsumi A, Yanagisawa H, Dohmae N, Hattori M, Ichijo H, Yan Z, Kikkawa M, Shirouzu M, Ishitani R, Nureki O
    • Journal Title

      Nat Struct Mol Biol.

      Volume: 25 Issue: 9 Pages: 797-804

    • DOI

      10.1038/s41594-018-0109-6

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A PP6-ASK3 Module Coordinates the Bidirectional Cell Volume Regulation under Osmotic Stress2018

    • Author(s)
      Watanabe Kengo、Umeda Tsuyoshi、Niwa Kuniyoshi、Naguro Isao、Ichijo Hidenori
    • Journal Title

      Cell Reports

      Volume: 22 Issue: 11 Pages: 2809-2817

    • DOI

      10.1016/j.celrep.2018.02.045

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The regulatory and signaling mechanisms of the ASK family2017

    • Author(s)
      Nishida Takuto、Hattori Kazuki、Watanabe Kengo
    • Journal Title

      Advances in Biological Regulation

      Volume: 66 Pages: 2-22

    • DOI

      10.1016/j.jbior.2017.05.004

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Presentation] ASK3 and cell volume regulation: common mechanism in cellular osmotic stress response and cell death induction2019

    • Author(s)
      渡邊謙吾
    • Organizer
      東京大学 医科学研究所 国際共同利用・共同拠点事業 平成30年度 若手研究者シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] ASK3不活性化における高浸透圧ストレスセンサー候補分子TRPML1の機能解析2018

    • Author(s)
      森下和浩,渡邊謙吾,一條秀憲
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ASK3 modulates cell volume under osmotic stress and beyond2018

    • Author(s)
      渡邊謙吾,一條秀憲
    • Organizer
      第10回シグナルネットワーク研究会
    • Related Report
      2018 Annual Research Report
  • [Presentation] PP6-ASK3 module is a key converter under bidirectional osmotic stress.2017

    • Author(s)
      Watanabe, K., Naguro, I. and Ichijo, H.
    • Organizer
      Consortium of Biological Sciences 2017 (ConBio2017)
    • Related Report
      2017 Research-status Report
  • [Presentation] NAMPT and RNF146 regulate the bidirectional cell volume regulator, ASK3.2017

    • Author(s)
      Watanabe, K., Naguro, I. and Ichijo, H.
    • Organizer
      FASEB Science Research Conferences: NAD+ Metabolism and Signaling
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Remarks] 東京大学 大学院薬学系研究科 細胞情報学教室 グループ紹介(渡邊グループ)

    • URL

      http://www.f.u-tokyo.ac.jp/~toxicol/html/group/WatanabeG.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 東京大学大学院 薬学系研究科・薬学部 プレスリリース

    • URL

      http://www.f.u-tokyo.ac.jp/topics.html?page=0&key=1521019111

    • Related Report
      2018 Annual Research Report
  • [Remarks] Cell Reports 2018年22巻11号 表紙

    • URL

      https://www.cell.com/cell-reports/issue?pii=S2211-1247(17)X0012-0

    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2020-03-30  

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