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Review
. 2011 May 27;4(1):20.
doi: 10.1186/1756-6606-4-20.

GPCR oligomers in pharmacology and signaling

Javier González-Maeso  1
Affiliations
Review

GPCR oligomers in pharmacology and signaling

Javier González-Maeso. Mol Brain. .

Abstract

G protein-coupled receptors (GPCRs) represent one of the largest families of cell surface receptors, and are the target of more than half of the current therapeutic drugs on the market. When activated by an agonist, the GPCR undergoes conformational changes that facilitate its interaction with heterotrimeric G proteins, which then relay signals to downstream intracellular effectors. Although GPCRs were thought to function as monomers, many studies support the hypothesis that G protein coupling involves the formation of GPCR homo- and/or hetero-complexes. These complex systems have been suggested to exhibit specific signaling cascades, pharmacological, internalization, and recycling properties. In this review, we summarize recent advances in our understanding of the structure, function and dynamics of GPCR complexes, as well as the findings obtained in animal models.

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Figures

Figure 1
Figure 1
G protein-dependent signaling and behavioral responses that require a GPCR heterocomplex. Hallucinogenic drugs, such as lysergic acid diethylamide (LSD), mescaline and psilocybin, all have in common a high affinity for the serotonin 5-HT2A receptor. Metabotropic glutamate 2 receptor (mGlu2) and serotonin 5-HT2A receptor form a specific functional GPCR heterocomplex in mammalian brain and in tissue culture preparations. mGlu2 transmembrane domains 4/5 mediate association with the 5-HT2A receptor. When 5-HT2A and mGlu2 are prevented from forming a receptor heterocomplex, activation of 5-HT2A by LSD elicits signaling characteristic of Gq/11-protein subtypes. In contrast, LSD acting at the 5-HT2A-mGlu2 receptor heterocomplex activates both Gq/11- and Gi/o-dependent signaling. Head-twitch behavior is reliably and robustly elicited by hallucinogenic 5-HT2A agonists, and is absent in mGlu2 knockout mice.
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