Muscarinic receptor oligomerization

Marsango, S., Ward, R. J., Alvarez-Curto, E. and Milligan, G. (2018) Muscarinic receptor oligomerization. Neuropharmacology, 136(Part C), pp. 401-410. (doi: 10.1016/j.neuropharm.2017.11.023) (PMID:29146505) (PMCID:PMC6078712)

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G protein-coupled receptors (GPCRs) have been classically described as monomeric entities that function by binding in a 1:1 stoichiometric ratio to both ligand and downstream signalling proteins. However, in recent years, a growing number of studies has supported the hypothesis that these receptors can interact to form dimers and higher order oligomers although the molecular basis for these interactions, the overall quaternary arrangements and the functional importance of GPCR oligomerization remain topics of intense speculation. Muscarinic acetylcholine receptors belong to class A of the GPCR family. Each muscarinic receptor subtype has its own particular distribution throughout the central and peripheral nervous systems. In the central nervous system, muscarinic receptors regulate several sensory, cognitive, and motor functions while, in the peripheral nervous system, they are involved in the regulation of heart rate, stimulation of glandular secretion and smooth muscle contraction. Muscarinic acetylcholine receptors have long been used as a model for the study of GPCR structure and function and to address aspects of GPCR dimerization using a broad range of approaches. In this review, the prevailing knowledge regarding the quaternary arrangement for the various muscarinic acetylcholine receptors has been summarized by discussing work ranging from initial results obtained using more traditional biochemical approaches to those generated with more modern biophysical techniques.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Alvarez-Curto, Dr Elisa and Ward, Dr Richard and Milligan, Professor Graeme and Marsango, Dr Sara
Authors: Marsango, S., Ward, R. J., Alvarez-Curto, E., and Milligan, G.
College/School:College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
Journal Name:Neuropharmacology
ISSN (Online):1873-7064
Published Online:14 November 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Neuropharmacology 136(Part C): 401-410
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
656901The organisational structure of class A GPCRs: Implications for pharmacology, function and therapeutic regulationGraeme MilliganMedical Research Council (MRC)MR/L023806/1RI MOLECULAR CELL & SYSTEMS BIOLOGY
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