Abstract
GABAB receptors are G-protein-coupled receptors that mediate inhibition throughout the central and peripheral nervous systems. A single cloned receptor, GABABR1, which has at least three alternatively spliced forms, appears to account for the vast majority of binding sites in the brain for high-affinity antagonists. In heterologous expression systems GABABR1 is poorly expressed on the plasma membrane and largely fails to couple to ion channels. A second gene, GABABR2, which exhibits moderately low homology to GABABR1, permits surface expression of GABABR1 and the appearance of baclofen-sensitive K+ and Ca+1 currents. We review the data that supports a model of the native GABAB receptor as a heterodimer composed of GABABR1 and GABABR2 proteins. New data from mutagenesis experiments are presented that point to amino acid residues on GABABR1 critical for ligand activation of the heterodimer. The possible role of GABABR2 in signal transduction is also discussed. The interdependent nature of the two subunits for receptor function makes the GABAB receptor a useful model to explore the larger significance of GPCR dimerization for G-protein activation.
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Jones, K., Tamm, J., Craig, D. et al. Signal Transduction by GABAB Receptor Heterodimers. Neuropsychopharmacol 23 (Suppl 1), S41–S49 (2000). https://doi.org/10.1016/S0893-133X(00)00145-7
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DOI: https://doi.org/10.1016/S0893-133X(00)00145-7
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