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Elucidating the function of GPCR dimerization by single-molecule observation

Research Project

Project/Area Number 24770120
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Functional biochemistry
Research InstitutionKyoto University

Principal Investigator

KASAI Rinshi  京都大学, 再生医科学研究所, 助教 (20447949)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2012: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Keywords生物物理 / 1分子計測 / Gタンパク質共役型受容体 / ダイマー形成 / 1分子計測
Research Abstract

As a result of the single fluorescent molecule observation of beta 2 adrenergic receptor (b2AR), we found that 1) it's under the dynamic dimer-monomer equilibrium in the plasma membrane even at the resting state, 2) the dimer lifetime is ~80 milliseconds, 3) agonist stimulation increases the dimer lifetime by 40%. By observing trimeric G-protein together with b2AR at the single molecule level, it was further found that trimeric G-protein temporarily binds to b2AR monomers as well as dimers with comparable lifetimes, ~20 milliseconds. These reversible binding-unbinding processes were not affected by agonist stimulation. The results obtained here indicate that G-protein signaling is regulated in such a dynamic manner.

Report

(3 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • Research Products

    (28 results)

All 2014 2013 2012 Other

All Journal Article (14 results) (of which Peer Reviewed: 14 results) Presentation (9 results) (of which Invited: 2 results) Book (4 results) Remarks (1 results)

  • [Journal Article] Single-molecule imaging revealed dynamic GPCR dimerization2014

    • Author(s)
      Kasai RS、Kusumi A
    • Journal Title

      Current Opinion in Cell Biology

      Volume: Vol. 27 Pages: 78-86

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Single-molecule imaging revealed dynamic GPCR dimerization2014

    • Author(s)
      R. S. Kasai and A. Kusumi
    • Journal Title

      Curr Opin Cell Biol.

      Volume: 27 Pages: 78-86

    • DOI

      10.1016/j.ceb.2013.11.008

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging2013

    • Author(s)
      Nagata KO、Nakada C、Kasai RS、Kusumi A、Ueda K
    • Journal Title

      Proceedings of the National Academy of Sciences of the United States of America

      Volume: Vol. 110 Pages: 5034-5039

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biocompatible fluorescent silicon nanocrystals for single-molecule tracking and fluorescence imaging2013

    • Author(s)
      Nishimura H、Ritchie K、Kasai RS、Goto M、Morone N、Sugimura H、Tanaka K、Sase I、Yoshimura A、Nakano Y、Fujiwara TK、Kusumi A
    • Journal Title

      Journal of Cell Biology

      Volume: Vol. 202 Pages: 967-983

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Single-Molecule Imaging of Receptor–Receptor Interactions2013

    • Author(s)
      Suzuki KGN、Kasai RS、Fujiwara TK、Kusumi A
    • Journal Title

      Methods in Cell Biology

      Volume: Vol. 117 Pages: 373-390

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biocompatible fluorescent silicon nanocrystals for single-molecule tracking and fluorescence imaging2013

    • Author(s)
      Nishimura H, Ritchie K, Kasai RS, Morone N, Sugimura H, Tanaka K, Sase I, Yoshimura A, Nakano Y, Fujiwara TK, and Kusumi A
    • Journal Title

      J Cell Biol.

      Volume: 202 Issue: 6 Pages: 967-83

    • DOI

      10.1083/jcb.201301053

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Single-molecule imaging of receptor-receptor interactions2013

    • Author(s)
      K. G. Suzuki, R. S. Kasai, T. K. Fujiwara, and A. Kusumi
    • Journal Title

      Methods Cell Biol.

      Volume: 117 Pages: 373-390

    • DOI

      10.1016/b978-0-12-408143-7.00020-7

    • ISBN
      9780124081437
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ABCA1 dimer-monomer interconversion during HDL generation revealed by single-molecule imaging.2013

    • Author(s)
      Nagata, K., O., Nakada, C.,, Kasai, R. S.,Kusumi, A. and Ueda, K.
    • Journal Title

      Proc Natl Acad Sci USA

      Volume: 110 Issue: 13 Pages: 5034-5039

    • DOI

      10.1073/pnas.1220703110

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Raf inhibitors target ras spatiotemporal dynamics2012

    • Author(s)
      Cho KJ、Kasai RS、Park JH、Chigurupati S、Heidorn SJ、van der Hoeven D、Plowman SJ、Kusumi A、Marais R、Hancock JF
    • Journal Title

      Current Biology

      Volume: Vol. 22 Pages: 945-955

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic organizing principles of the plasma membrane that regulate signal transduction : commemorating the fortieth anniversary of Singer and Nicolson's fluid-mosaic model2012

    • Author(s)
      Kusumi A、Fujiwara TK、Chadda R、Xie M、Tsunoyama TA、Kalay Z、Kasai RS、Suzuki KGN
    • Journal Title

      Annual Review of Cell and Developmental Biology

      Volume: Vol. 28 Pages: 215-250

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Membrane mechanisms for signal transduction : the coupling of the meso-scale raft domains to membrane-skeleton-induced compartments and dynamic protein complexes2012

    • Author(s)
      Kusumi A、Fujiwara TK、Morone N、Yoshida KJ、Chadda R、Xie M、Kasai RS、Suzuki KGN
    • Journal Title

      Seminars in Cell & Developmental Biology

      Volume: Vol. 23 Pages: 164-144

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transient GPI-anchored protein homodimers are units for raft organization and function2012

    • Author(s)
      Suzuki KGN、Kasai RS、Hirosawa KM、Nemoto YL、Ishibashi M、Miwa Y、Fujiwara TK、Kusumi A
    • Journal Title

      Nature Chemical Biology

      Volume: Vol. 8 Pages: 774-783

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Transient GPI-anchored protein homodimers are units for raft organization and function2012

    • Author(s)
      K. G. N. Suzuki, R. S. Kasai, K. M. Hirosawa, Y. L. Nemoto, M. Ishibashi, Y. Miwa, T. K. Fujiwara, and A. Kusumi
    • Journal Title

      Nat. Chem. Biol.

      Volume: 8 Issue: 9 Pages: 774-783

    • DOI

      10.1038/nchembio.1028

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Raf inhibitors target Ras spatiotemporal dynamics2012

    • Author(s)
      K. J. Cho, R. S. Kasai, J. H. Park, S. Chigurupati, S. J. Heidorn, D. van der Hoeven, S. J. Plowman, A. Kusumi, R. Marais, and J. F. Hancock
    • Journal Title

      Curr. Biol.

      Volume: 22 Issue: 11 Pages: 945-955

    • DOI

      10.1016/j.cub.2012.03.067

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] GPCR dimers as active signal triggers : inverse agonist effects revealed by single-molecule imaging analysis2013

    • Author(s)
      Kasai RS, Fujiwara TK, Kusumi A
    • Organizer
      第51回日本生物物理学会年回
    • Place of Presentation
      京都
    • Year and Date
      2013-10-30
    • Related Report
      2013 Final Research Report
  • [Presentation] Transient GPCR dimers trigger signaling as revealed by single-molecule imaging2013

    • Author(s)
      Kasai RS, Kusumi A
    • Organizer
      The 2013 Cold Spring Harbor Asia Conference"NEW ADVANCES IN OPTICAL IMAGING OF LIVE CELLS & ORGANISMS"
    • Place of Presentation
      蘇州中国
    • Year and Date
      2013-08-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Dynamic Monomer-Dimer Equilibrium as a General Property of the Class A GPCR : Single-Molecule Imaging Study2013

    • Author(s)
      Kasai RS
    • Organizer
      The 14th Membrane Research Forum
    • Place of Presentation
      京都
    • Year and Date
      2013-03-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Transient GPCR dimers trigger signaling as revealed by single-molecule imaging2013

    • Author(s)
      Kasai RS, Kusumi A
    • Organizer
      The 2013 Cold Spring Harbor Asia Conference “NEW ADVANCES IN OPTICAL IMAGING OF LIVE CELLS & ORGANISMS”
    • Place of Presentation
      蘇州 中国
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] GPCR dimers as active signal triggers: inverse agonist effects revealed by single-molecule imaging analysis2013

    • Author(s)
      Rinshi S. Kasai, Takahiro K. Fujiwara, and Akihiro Kusumi
    • Organizer
      日本生物物理学会 第51回年回
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Presentation] Dynamic Monomer-Dimer Equilibrium as a General Property of the Class A GPCR: Single-Molecule Imaging Study2013

    • Author(s)
      Kasai RS
    • Organizer
      The 14th Membrane Research Forum
    • Place of Presentation
      京都
    • Related Report
      2012 Research-status Report
    • Invited
  • [Presentation] Dynamic monomer-dimer equilibrium as a general property of the class A GPCR : detection by single-molecule imaging2012

    • Author(s)
      Kasai RS, Fujiwara TK, Kusumi A
    • Organizer
      The 2012 American Society for Cell Biology Annual Meeting / ASCB 52th Annual Meeting
    • Place of Presentation
      サンフランシスコアメリカ
    • Year and Date
      2012-12-16
    • Related Report
      2013 Final Research Report
  • [Presentation] Single-molecule imaging revealed acceleration of trimeric G-protein turnover by transient dimerization of ligandedβ2-AR2012

    • Author(s)
      Kasai RS
    • Organizer
      第50回日本生物物理学会年回
    • Place of Presentation
      名古屋
    • Year and Date
      2012-09-22
    • Related Report
      2013 Final Research Report
  • [Presentation] Dynamic monomer-dimer equilibrium as a general property of the class A GPCR: detection by single-molecule imaging2012

    • Author(s)
      Kasai RS, Fujiwara TK, Kusumi A
    • Organizer
      The 2012 American Society for Cell Biology Annual Meeting
    • Place of Presentation
      San Francisco, U.S.A.
    • Related Report
      2012 Research-status Report
  • [Book] "1分子イメジングにより明らかになった, GPCRのモノマー・ダイマーの動的な交換"、Clinical Neuroscience月刊臨床神経科学2013

    • Author(s)
      笠井倫志
    • Publisher
      中外医学社
    • Related Report
      2013 Final Research Report
  • [Book] 超高速・超解像1蛍光分子顕微鏡"、現代化学2013

    • Author(s)
      藤原敬宏、笠井倫志、楠見明弘
    • Publisher
      東京化学同人
    • Related Report
      2013 Final Research Report
  • [Book] Annu. Rev. Cell Dev. Biol., Volume 282012

    • Author(s)
      Kusumi A, Fujiwara TK, Chadda R, Xie M, Tsunoyama TA, Kalay Z, Kasai RS, Suzuki KGN
    • Total Pages
      36
    • Publisher
      Annual Reviews
    • Related Report
      2012 Research-status Report
  • [Book] Semin. Cell Dev. Biol., Volume 232012

    • Author(s)
      Kusumi A, Fujiwara TK, Morone N, Yoshida KJ, Chadda R, Xie M, Kasai RS, Suzuki KGN
    • Total Pages
      19
    • Publisher
      Elsevier
    • Related Report
      2012 Research-status Report
  • [Remarks]

    • URL

      http://www.nanobio.frontier.kyoto-u.ac.jp/

    • Related Report
      2013 Final Research Report

URL: 

Published: 2013-05-31   Modified: 2019-07-29  

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