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The Class-A GPCR Dopamine D2 Receptor Forms Transient Dimers Stabilized by Agonists: Detection by Single-Molecule Tracking.

Authors
  • Kasai, Rinshi S1
  • Ito, Shuichi V1
  • Awane, Ryo M1
  • Fujiwara, Takahiro K2
  • Kusumi, Akihiro3, 4, 5
  • 1 Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan. , (Japan)
  • 2 Center for Meso-Bio Single-Molecule Imaging (CeMI), Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, 606-8507, Japan. , (Japan)
  • 3 Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, 606-8507, Japan. [email protected] , (Japan)
  • 4 Center for Meso-Bio Single-Molecule Imaging (CeMI), Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Kyoto, 606-8507, Japan. [email protected] , (Japan)
  • 5 Membrane Cooperativity Unit, Okinawa Institute of Science and Technology, Okinawa, 904-0495, Japan. [email protected] , (Japan)
Type
Published Article
Journal
Cell Biochemistry and Biophysics
Publisher
Springer-Verlag
Publication Date
Nov 07, 2017
Identifiers
DOI: 10.1007/s12013-017-0829-y
PMID: 29116599
Source
Medline
Keywords
License
Unknown

Abstract

Whether class-A G-protein coupled receptors (GPCRs) exist and work as monomers or dimers has drawn extensive attention. A class-A GPCR dopamine D2 receptor (D2R) is involved in many physiological and pathological processes and diseases, indicating its critical role in proper functioning of neuronal circuits. In particular, D2R homodimers might play key roles in schizophrenia development and amphetamine-induced psychosis. Here, using single-molecule imaging, we directly tracked single D2R molecules in the plasma membrane at a physiological temperature of 37 °C, and unequivocally determined that D2R forms transient dimers with a lifetime of 68 ms in its resting state. Agonist addition prolonged the dimer lifetime by a factor of ~1.5, suggesting the possibility that transient dimers might be involved in signaling.

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