The muscarinic M3acetylcholine receptor exists as two differently sized complexes at the plasma membrane

Patowary, S., Alvarez-Curto, E. , Xu, T.-R., Holz, J.D., Oliver, J.A., Milligan, G. and Raicu, V. (2013) The muscarinic M3acetylcholine receptor exists as two differently sized complexes at the plasma membrane. Biochemical Journal, 452(2), pp. 303-312. (doi:10.1042/BJ20121902)

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Publisher's URL: http://dx.doi.org/10.1042/BJ20121902

Abstract

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milligan, Professor Graeme and Xu, Professor Tianrui and Alvarez-Curto, Dr Elisa
Authors: Patowary, S., Alvarez-Curto, E., Xu, T.-R., Holz, J.D., Oliver, J.A., Milligan, G., and Raicu, V.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Biochemical Journal
Publisher:Portland Press Ltd.
ISSN:0264-6021
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
510631The organisational structure of class A GPCRs: implications for function and drug designGraeme MilliganMedical Research Council (MRC)G0900050RI NEUROSCIENCE & PSYCHOLOGY
437051Exploring the selectivity and consequences of GPCR homo and hetero dimerisation/oligomerisation using receptors activated solely by ......Graeme MilliganBiotechnology and Biological Sciences Research Council (BBSRC)BB/E006302/1RI NEUROSCIENCE & PSYCHOLOGY