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Previous Article | Next Article
The Journal of Neuroscience, October 15, 2001, 21(20):8043-8052
GABAB2 Is Essential for G-Protein Coupling of the GABAB Receptor Heterodimer
Melanie J. Robbins2, Andrew R. Calver1, Alexander K. Filippov4, Warren D. Hirst1, Robert B. Russell3, Martyn D. Wood2, Shabina Nasir1, Andrés Couve4, 5, David A. Brown4, Stephen J. Moss4, 5, and Menelas N. Pangalos1 Departments of 1 Neurology Centre of Excellence for Drug Discovery (CEDD) and 2 Psychiatry CEDD and 3 Bioinformatics Research Group, GlaxoSmithKline Pharmaceuticals, Harlow, Essex CM19 5AW, United Kingdom, and 4 Department of Pharmacology and 5 Medical Research Council Laboratory for Molecular Cell Biology, University College London, London WC1E 6BT, United Kingdom
GABAB receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABAB1 and GABAB2, for functional expression. Whereas GABAB1 is capable of binding receptor agonists and antagonists, the role of each GABAB subunit in receptor signaling is unknown. Here we identified amino acid residues within the second intracellular domain of GABAB2 that are critical for the coupling of GABAB receptor heterodimers to their downstream effector systems. Our results provide strong evidence for a functional role of the GABAB2 subunit in G-protein coupling of the GABAB receptor heterodimer. In addition, they provide evidence for a novel "sequential" GPCR signaling mechanism in which ligand binding to one heterodimer subunit can induce signal transduction through the second partner of a heteromeric complex.
Key words: GABAB; GPCR; dimerization; signaling; G-protein coupling; receptor subunits
Copyright © 2001 Society for Neuroscience 0270-6474/01/21208043-10$05.00/0
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