Molecular aspects of muscarinic receptor dimerization

The five muscarinic acetylcholine receptors (M-1-M-5) are prototypical memb ers of the superfamily of G-protein-coupled receptors (GPCRs). During the p ast decade, this laboratory has used different members oft his receptor sub family as model systems to study the molecular mechanisms involved in GPCR function. This article reviews recent investigations dealing with molecular aspects of M-3 muscarinic receptor assembly and dimerization/oligomerizati on. Studies with coexpressed M-3 receptor/fragments and M-3 muscarinic/alph a(2C)-adrenergic hybrid receptors showed that muscarinic receptors, like ot her GPCRs, are composed of multiple autonomous folding domains. Moreover, b iochemical studies have provided direct evidence for the formation of M-3 r eceptor dimers/oligomers. These high molecular mass receptor species ave ex pressed on the cell surface and can bind muscarinic ligands. M-3 receptor d imerization/oligomerization appears to be receptor subtype-selective and in volves both noncovalent interactions as well as disulfide-crosslinking of r eceptor monomers. These studies add to the growing number of reports sugges ting the existence of GPCR dimers or multimers. The precise functional char acteristics of such receptor aggregates remain to be elucidated. (C) 2000 A merican College of Neuropsychopharmacology. Published by Elsevier Science I nc.