Journal
EMBO JOURNAL
Volume 30, Issue 12, Pages 2336-2349Publisher
WILEY
DOI: 10.1038/emboj.2011.143
Keywords
cooperativity; GABA; GABA(B); GPCR; receptor oligomer
Categories
Funding
- CNRS
- INSERM
- Cisbio
- French Ministry of Research, Agence Nationale de la Recherche [ANR-06-BLAN-0087, ANR-09-BLAN-0272]
- Senomyx
- Swiss Science Foundation [3100A0-117816]
- European Community [201714]
- French government
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0272, ANR-06-BLAN-0087] Funding Source: Agence Nationale de la Recherche (ANR)
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G protein-coupled receptors (GPCRs) have key roles in cell-cell communication. Recent data suggest that these receptors can form large complexes, a possibility expected to expand the complexity of this regulatory system. Among the brain GPCRs, the heterodimeric GABA(B) receptor is one of the most abundant, being distributed in most brain regions, on either pre- or post-synaptic elements. Here, using specific antibodies labelled with time-resolved FRET compatible fluorophores, we provide evidence that the heterodimeric GABA(B) receptor can form higher-ordered oligomers in the brain, as suggested by the close proximity of the GABA(B1) subunits. Destabilizing the oligomers using a competitor or a GABA(B1) mutant revealed different G protein coupling efficiencies depending on the oligomeric state of the receptor. By examining, in heterologous system, the G protein coupling properties of such GABA(B) receptor oligomers composed of a wild-type and a non-functional mutant heterodimer, we provide evidence for a negative functional cooperativity between the GABA(B) heterodimers. The EMBO Journal (2011) 30, 2336-2349. doi: 10.1038/emboj.2011.143; Published online 6 May 2011
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