The literature on GPCR (G-protein-coupled receptor) homo-oligomerization encompasses conflicting views that range from interpretations that GPCRs must be monomeric, through comparatively newer proposals that they exist as dimers or higher-order oligomers, to suggestions that such quaternary structures are rather ephemeral or merely accidental and may serve no functional purpose. In the present study we use a novel method of FRET (Förster resonance energy transfer) spectrometry and controlled expression of energy donor-tagged species to show that M3Rs (muscarinic M3 acetylcholine receptors) at the plasma membrane exist as stable dimeric complexes, a large fraction of which interact dynamically to form tetramers without the presence of trimers, pentamers, hexamers etc. That M3R dimeric units interact dynamically was also supported by co-immunoprecipitation of receptors synthesized at distinct times. On the basis of all these findings, we propose a conceptual framework that may reconcile the conflicting views on the quaternary structure of GPCRs.
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Research Article|
May 10 2013
The muscarinic M3 acetylcholine receptor exists as two differently sized complexes at the plasma membrane
Suparna Patowary;
Suparna Patowary
1
*Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
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Elisa Alvarez-Curto;
Elisa Alvarez-Curto
1
†Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Tian-Rui Xu;
Tian-Rui Xu
2
†Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Jessica D. Holz;
Jessica D. Holz
*Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
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Julie A. Oliver;
Julie A. Oliver
‡Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
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Graeme Milligan;
Graeme Milligan
†Molecular Pharmacology Group, Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8QQ, Scotland, U.K.
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Valerică Raicu
*Physics Department, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
‡Department of Biological Sciences, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, U.S.A.
4To whom correspondence should be addressed (email vraicu@uwm.edu).
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Publisher: Portland Press Ltd
Received:
January 02 2013
Revision Received:
March 01 2013
Accepted:
March 25 2013
Accepted Manuscript online:
March 25 2013
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2013 Biochemical Society
2013
Biochem J (2013) 452 (2): 303–312.
Article history
Received:
January 02 2013
Revision Received:
March 01 2013
Accepted:
March 25 2013
Accepted Manuscript online:
March 25 2013
Citation
Suparna Patowary, Elisa Alvarez-Curto, Tian-Rui Xu, Jessica D. Holz, Julie A. Oliver, Graeme Milligan, Valerică Raicu; The muscarinic M3 acetylcholine receptor exists as two differently sized complexes at the plasma membrane. Biochem J 1 June 2013; 452 (2): 303–312. doi: https://doi.org/10.1042/BJ20121902
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