Journal
BASIC & CLINICAL PHARMACOLOGY & TOXICOLOGY
Volume 126, Issue -, Pages 25-34Publisher
WILEY
DOI: 10.1111/bcpt.13241
Keywords
GABA; GABA-B; GABA(B) receptors; proteomics; gamma-aminobutyric acid
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GABA(B) receptors (GBRs), the G protein-coupled receptors for the neurotransmitter gamma-aminobutyric acid (GABA), regulate synaptic transmission at most synapses in the brain. Proteomic approaches revealed that native GBR complexes assemble from an inventory of ~30 proteins that provide a molecular basis for the functional diversity observed with these receptors. Studies with reconstituted GBR complexes in heterologous cells and complementary knockout studies have allowed to identify cellular and physiological functions for obligate and several non-obligate receptor components. It emerges that modular association of receptor components in space and time generates a variety of multiprotein receptor complexes with different localizations, kinetic properties and effector channels. This article summarizes current knowledge on the organizing principle of GBR complexes. We further discuss unanticipated receptor functions, links to disease and opportunities for drug discovery arising from the identification of novel receptor components.
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