4.7 Review

Muscarinic receptor oligomerization

Journal

NEUROPHARMACOLOGY
Volume 136, Issue -, Pages 401-410

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2017.11.023

Keywords

Muscarinic acetylcholine receptor; Quaternary structure; Dimerization; Oligomerization; Ligand regulation

Funding

  1. Medical Research Council [MR/L023806/1, G0900050]
  2. Biotechnology and Biological Sciences Research Council [BK006302/1]
  3. BBSRC [BB/E006302/1] Funding Source: UKRI
  4. MRC [MR/L023806/1, G0900050] Funding Source: UKRI
  5. Biotechnology and Biological Sciences Research Council [BB/E006302/1] Funding Source: researchfish
  6. Medical Research Council [MR/L023806/1, G0900050] Funding Source: researchfish

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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. This article is part of the Special Issue entitled 'Neuropharmacology on Muscarinic Receptors'. (C) 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

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