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Psychiatric disorders

Double GPCR trouble

Nature Reviews Neuroscience volume 9, page 253 (2008)Cite this article

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It has been suggested that many members of the G-protein-coupled receptor (GPCR) family can exist as oligomeric complexes. Two findings led the authors to posit that this could occur with 5-HT2AR and mGluR2: mRNA for the two receptors was colocalized in mouse neuronal cultures, and mGluR2 protein levels were decreased in 5-HT2AR-knockout mice. Evidence for the existence of 5-HT2AR–mGluR2 complexes was obtained by co-immunoprecipitation and resonance-energy-transfer studies.

Competition-binding experiments, in which an mGluR2/3 agonist increased the affinity of three hallucinogenic 5-HT2AR agonists for the 5-HT-binding site, and in which a 5-HT2AR agonist decreased the affinity of the three mGluR2/3 agonists for the glutamate-binding site, suggested that the 5-HT2AR–mGluR2 complex might serve to integrate serotonin and glutamate signalling. Furthermore, by measuring the regulation of specific G-protein subunits, the receptor complex was shown to modulate G-protein coupling. Using molecular chimaeras of mGluR2 and mGluR3 — the latter of which did not form complexes — the authors demonstrated that the segment of mGluR2 that contains transmembrane helices 4 and 5 was necessary and sufficient for the formation of a complex with 5-HT2AR.

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ORIGINAL RESEARCH PAPER

  1. González-Maeso, J. et al. Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452, 93–97 (2008)

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  1. Charlotte Harrison
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Harrison, C. Double GPCR trouble. Nat Rev Neurosci 9, 253 (2008). https://doi.org/10.1038/nrn2362

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  • DOI: https://doi.org/10.1038/nrn2362

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