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PMID: 17965750 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

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 ·Vol. 153 Suppl 1 ·2008-03-00 ·Pages S216-29

Milligan G

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.

MeSH Terms
Animals Dimerization Humans Ligands Protein Structure, Quaternary Receptors, G-Protein-Coupled/biosynthesis,drug effects,metabolism,physiology Receptors, Glutamate/metabolism,physiology Rhodopsin/metabolism Structure-Activity Relationship
Chemicals
Ligands Receptors, G-Protein-Coupled Receptors, Glutamate Rhodopsin
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Milligan G
Molecular Pharmacology Group, Division of Biochemistry and Molecular Biology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland, UK. [email protected]
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Article Info
Journal
British journal of pharmacology
Abbr.
Br J Pharmacol
ISSN
0007-1188
DOI
10.1038/sj.bjp.0707490
Email
[email protected]
Published
2008-03-00
Epub
2007-00-29
Pages
S216-29
Language
English
Region
England
NLM ID
7502536
PMCID
PMC2268067
Subset
IM
Grants
Medical Research Council · G9811527 · United Kingdom
Wellcome Trust · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
External Links
PubMed source DOI: 10.1038/sj.bjp.0707490 PMC Full Text View journal details
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