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PMID: 11588177 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

GABA(B2) is essential for g-protein coupling of the GABA(B) receptor heterodimer.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 20 ·2001-10-15 ·Pages 8043-52

Robbins MJ, Calver AR, Filippov AK, Hirst WD, Russell RB, Wood MD, Nasir S, Couve A, Brown DA, Moss SJ, Pangalos MN

Abstract

GABA(B) receptors are unique among G-protein-coupled receptors (GPCRs) in their requirement for heterodimerization between two homologous subunits, GABA(B1) and GABA(B2), for functional expression. Whereas GABA(B1) is capable of binding receptor agonists and antagonists, the role of each GABA(B) subunit in receptor signaling is unknown. Here we identified amino acid residues within the second intracellular domain of GABA(B2) that are critical for the coupling of GABA(B) receptor heterodimers to their downstream effector systems. Our results provide strong evidence for a functional role of the GABA(B2) subunit in G-protein coupling of the GABA(B) 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.

MeSH Terms
Amino Acids/genetics,metabolism Animals Calcium/metabolism Cells, Cultured Dimerization GTP-Binding Proteins/metabolism Humans Kidney/cytology,metabolism Microinjections Mutagenesis, Site-Directed Patch-Clamp Techniques Protein Binding/physiology Protein Subunits Rats Receptors, GABA/genetics,metabolism Receptors, GABA-B/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Sequence Analysis, Protein Signal Transduction/physiology Structure-Activity Relationship Superior Cervical Ganglion/cytology,metabolism Transfection
Chemicals
Amino Acids GABA type B receptor, subunit 1 GABBR2 protein, human Gabbr2 protein, rat Protein Subunits Receptors, GABA Receptors, GABA-B Recombinant Fusion Proteins GTP-Binding Proteins Calcium
Authors & Affiliations
11 authors, click to expand affiliations / ORCID
Robbins M J
Department Psychiatry CEDD, GlaxoSmithKline Pharmaceuticals, Harlow, Essex CM19 5AW, United Kingdom.
Calver A R
Filippov A K
Hirst W D
Russell R B
Wood M D
Nasir S
Couve A
Brown D A
Moss S J
Pangalos M N
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-10-15
Pages
8043-52
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6763845
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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