The muscarinic M3acetylcholine receptor exists as two differently sized complexes at the plasma membrane (original) (raw)

Patowary, S., Alvarez-Curto, E. ORCID: https://orcid.org/0000-0003-4004-4545, Xu, T.-R., Holz, J.D., Oliver, J.A., Milligan, Graeme ORCID: https://orcid.org/0000-0002-6946-3519 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) (PMID:23521066)

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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.

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Funder and Project Information

1

The organisational structure of class A GPCRs: implications for function and drug design

Graeme Milligan

G0900050

RI NEUROSCIENCE & PSYCHOLOGY

1

Exploring the selectivity and consequences of GPCR homo and hetero dimerisation/oligomerisation using receptors activated solely by ......

Graeme Milligan

BB/E006302/1

RI NEUROSCIENCE & PSYCHOLOGY

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