Oligomerization of a G protein-coupled receptor in neurons controlled by its structural dynamics

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Thor C Møller, Jerome Hottin, Caroline Clerté, Jurriaan M Zwier, Thierry Durroux, Philippe Rondard, Laurent Prézeau, Catherine A Royer, Jean-Philippe Pin, Emmanuel Margeat, Julie Kniazeff

G protein coupled receptors (GPCRs) play essential roles in intercellular communication. Although reported two decades ago, the assembly of GPCRs into dimer and larger oligomers in their native environment is still a matter of intense debate. Here, using number and brightness analysis of fluorescently labeled receptors in cultured hippocampal neurons, we confirm that the metabotropic glutamate receptor type 2 (mGlu2) is a homodimer at expression levels in the physiological range, while heterodimeric GABAB receptors form larger complexes. Surprisingly, we observed the formation of larger mGlu2 oligomers upon both activation and inhibition of the receptor. Stabilizing the receptor in its inactive conformation using biochemical constraints also led to the observation of oligomers. Following our recent observation that mGlu receptors are in constant and rapid equilibrium between several states under basal conditions, we propose that this structural heterogeneity limits receptor oligomerization. Such assemblies are expected to stabilize either the active or the inactive state of the receptor.

Original languageEnglish
JournalScientific Reports
Volume8
Issue number1
Pages (from-to)10414
ISSN2045-2322
DOIs
Publication statusPublished - 10 Jul 2018
Externally publishedYes

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