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Nature 1998 Dec 17;3966712:674-9. doi: 10.1038/25348.
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GABA(B) receptors function as a heteromeric assembly of the subunits GABA(B)R1 and GABA(B)R2.

Jones KA , Borowsky B , Tamm JA , Craig DA , Durkin MM , Dai M , Yao WJ , Johnson M , Gunwaldsen C , Huang LY , Tang C , Shen Q , Salon JA , Morse K , Laz T , Smith KE , Nagarathnam D , Noble SA , Branchek TA , Gerald C .

The principal inhibitory neurotransmitter GABA (gamma-aminobutyric acid) exerts its effects through two ligand-gated channels, GABA(A) and GABA(C) receptors, and a third receptor, GABA(B) , which acts through G proteins to regulate potassium and calcium channels. Cells heterologously expressing the cloned DNA encoding the GABA(B)R1 protein exhibit high-affinity antagonist-binding sites, but they produce little of the functional activity expected from studies of endogenous GABA(B) receptors in the brain. Here we describe a new member of the GABA(B) polypeptide family, GABA(B)R2, that shows sequence homology to GABA(B)R1. Neither GABA(B)R1 nor GABA(B)R2, when expressed individually, activates GIRK-type potassium channels; however, the combination of GABA(B)R1 and GABA(B)R2 confers robust stimulation of channel activity. Both genes are co-expressed in individual neurons, and both proteins co-localize in transfected cells. Moreover, immunoprecipitation experiments indicate that the two polypeptides associate with each other, probably as heterodimers. Several G-protein-coupled receptors (GPCRs) exist as high-molecular-weight species, consistent with the formation of dimers by these receptors, but the relevance of these species for the functioning of GPCRs has not been established. We have now shown that co-expression of two GPCR structures, GABA(B)R1 and GABA(B)R2, belonging to the same subfamily is essential for signal transduction by GABA(B) receptors.

PubMed ID: 9872315
Article link: Nature

Species referenced: Xenopus
Genes referenced: gabbr1 gabbr2 gprc6a kcnj3