A day in the life of a G protein-coupled receptor: the contribution to function of G protein-coupled receptor dimerization

Milligan, G. (2008) A day in the life of a G protein-coupled receptor: the contribution to function of G protein-coupled receptor dimerization. British Journal of Pharmacology, 153(.), S216-S229. (doi: 10.1038/sj.bjp.0707490)

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Publisher's URL: http://dx.doi.org/10.1038/sj.bjp.0707490

Abstract

G protein-coupled receptors are one of the most actively studied families of proteins. However, despite the ubiquity of protein dimerization and oligomerization as a structural and functional motif in biology, until the last decade they were generally considered as monomeric, non-interacting polypeptides. For the metabotropic glutamate-like group of G protein-coupled receptors, it is now firmly established that they exist and function as dimers or, potentially, even within higher-order structures. Despite some evidence continuing to support the view that rhodopsin-like G protein-coupled receptors are predominantly monomers, many recent studies are consistent with the dimerization/oligomerization of such receptors. Key roles suggested for dimerization of G protein-coupled receptors include control of protein maturation and cell surface delivery and providing the correct framework for interactions with both hetero-trimeric G proteins and arrestins to allow signal generation and its termination. As G protein-coupled receptors are the most targeted group of proteins for the development of therapeutic small molecule medicines, recent indications that hetero-dimerization between co-expressed G protein-coupled receptors may be a common process offers the potential for the development of more selective and tissue restricted medicines. However, many of the key experiments have, so far, been limited to model cell systems. Priorities for the future include the generation of tools and reagents able to identify unequivocally potential G protein-coupled receptor hetero-dimers in native tissues and detailed analyses of the influence of hetero-dimerization on receptor function and pharmacology

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Milligan, Professor Graeme
Authors: Milligan, G.
Subjects:R Medicine > RM Therapeutics. Pharmacology
College/School:College of Medical Veterinary and Life Sciences > Institute of Neuroscience and Psychology
Journal Name:British Journal of Pharmacology
Publisher:John Wiley & Sons, Inc.
ISSN:0007-1188
ISSN (Online):1476-5381
Published Online:29 January 2009
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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
242491Quantitative Analysis of the Effects of Receptor and G-Protein Mutations and Polymorphisms on Signal InitiationGraeme MilliganMedical Research Council (MRC)G9811527Institute of Neuroscience and Psychology
242492Quantitative Analysis of the Effects of Receptor and G-Protein Mutations and Polymorphisms on Signal InitiationGraeme MilliganMedical Research Council (MRC)G9811527Institute of Neuroscience and Psychology
389781The quaternary structure of G-protein coupled receptors - implications for function drug design. Programme grant support renewalGraeme MilliganMedical Research Council (MRC)G9811527Institute of Neuroscience and Psychology