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

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.

journal_name

Br J Pharmacol

journal_title

British journal of pharmacology

authors

Milligan G

doi

10.1038/sj.bjp.0707490

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

S216-29

eissn

0007-1188

issn

1476-5381

pii

0707490

journal_volume

153 Suppl 1

pub_type

杂志文章,评审

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