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The physiological ligand and activation mechanisms of an orphan metabotropic receptor Prrt3

Research Project

Project/Area Number 16K18999
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field General physiology
Research InstitutionNational Institute for Physiological Sciences

Principal Investigator

Chen I-Shan  生理学研究所, 分子細胞生理研究領域, 特任助教 (40757770)

Research Collaborator KUBO Yoshihiro  生理学研究所, 教授
TATEYAMA Michihiro  生理学研究所, 准教授
YAMAMOTO Tomomi  生理学研究所, 技術職員
FUKATA Yuko  生理学研究所, 准教授
UESUGI Motonari  京都大学, 教授
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsLigand / GPCR / Receptor / 生理学
Outline of Final Research Achievements

Prrt3 is an orphan family C metabotropic receptor. There is no publication concerning Prrt3 and the physiological roles and functioning mechanisms of Prrt3 are totally unknown. In the present study, we aim to clarify the physiological ligand and activation mechanisms of Prrt3. We performed molecular biological, electrophysiological and [Ca2+]i imaging experiments using Xenopus oocytes and HEK293 cells, and we observed the following results: (1) Gi/o, but not Gq, is coupled with Prrt3; (2) Prrt3 is not activated by the cleavage of its N-terminal extracellular domain; (3) some muscarinic receptor agonists, but not ACh, slightly activates the Prrt3; (4) we happened to identify a novel activator of GIRK channel, ivermectin.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (9 results)

All 2018 2017 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (6 results) (of which Int'l Joint Research: 1 results) Remarks (1 results)

  • [Journal Article] Ivermectin and its target molecules: shared and unique modulation mechanisms of ion channels and receptors by ivermectin.2018

    • Author(s)
      Chen IS, Kubo Y.
    • Journal Title

      J Physiol

      Volume: 印刷中 Issue: 10 Pages: 1833-1845

    • DOI

      10.1113/jp275236

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ivermectin activates GIRK channels in a PIP2 -dependent, Gβγ-independent manner and an amino acid residue at the slide helix governs the activation.2017

    • Author(s)
      Chen, I.S., Tateyama, M., Fukata, Y., Uesugi, M., & Kubo, Y.
    • Journal Title

      Journal of Physiology

      Volume: 595 Issue: 17 Pages: 5895-5912

    • DOI

      10.1113/jp274871

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Presentation] Effects and activation mechanisms of ivermectin on G-protein-gated inwardly rectifying potassium channels2018

    • Author(s)
      I-Shan Chen, Michihiro Tateyama, Yuko Fukata, Motonari Uesugi, Yoshihiro Kubo
    • Organizer
      The 62nd Annual Meeting of the Biophysical Society
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel regulation mechanisms of the GIRK channel activity by small molecules2018

    • Author(s)
      I-Shan Chen, Yoshihiro Kubo
    • Organizer
      第95回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Behavioral analyses of forebrain specific knock-out mice of an orphan metabotropic receptor Prrt3 and screening of small molecule library toward identification of its ligand2017

    • Author(s)
      I-Shan Chen
    • Organizer
      The 40th Annual Meeting of the Japan Neuroscience Society
    • Place of Presentation
      Makuhari Messe, chiba, chiba
    • Year and Date
      2017-07-20
    • Related Report
      2016 Research-status Report
  • [Presentation] Effects and activation mechanisms of antiparasitic agents on GIRK channels2017

    • Author(s)
      I-Shan Chen, Yoshihiro Kubo
    • Organizer
      第94回日本生理学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Behavioral analyses of forebrain specific knock-out mice of an orphan metabotropic receptor Prrt3 and screening of small molecule library toward identification of its ligand2017

    • Author(s)
      I-Shan Chen, Tomomi Yamamoto, Li Zhou, Rie Natsume, Kohtaro Konno, Motonari Uesugi, Masahiko Watanabe, Keizo Takao, Tsuyoshi Miyakawa, Kenji Sakimura, Yoshihiro Kubo
    • Organizer
      第40回日本神経科学大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Activation mechanisms of G-protein-gated inwardly rectifying K+ channel by ivermectin2017

    • Author(s)
      I-Shan Chen, Michihiro Tateyama, Yuko Fukata, Motonari Uesugi, Yoshihiro Kubo
    • Organizer
      第64回中部日本生理学会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 研究報告:抗寄生虫剤イベルメクチンによるGIRKチャネルの活性化機構の解明

    • URL

      http://www.nips.ac.jp/nips_research/2017/08/girk.html

    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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