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GABAB receptors : physiological functions and mechanisms of diversity

Pinard, Audrée and Seddik, Riad and Bettler, Bernhard. (2010) GABAB receptors : physiological functions and mechanisms of diversity. Advances in pharmacology, Vol. 58. pp. 231-255.

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Official URL: http://edoc.unibas.ch/dok/A6007622

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Abstract

GABA(B) receptors are the G-protein-coupled receptors (GPCRs) for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the central nervous system. GABA(B) receptors are implicated in the etiology of a variety of psychiatric disorders and are considered attractive drug targets. With the cloning of GABA(B) receptor subunits 13 years ago, substantial progress was made in the understanding of the molecular structure, physiology, and pharmacology of these receptors. However, it remained puzzling that native studies demonstrated a heterogeneity of GABA(B) responses that contrasted with a very limited diversity of cloned GABA(B) receptor subunits. Until recently, the only firmly established molecular diversity consisted of two GABA(B1) subunit isoforms, GABA(B1a) and GABA(B1b), which assemble with GABA(B2) subunits to generate heterodimeric GABA(B(1a,2)) and GABA(B(1b,2)) receptors. Using genetic, ultrastructural, biochemical, and electrophysiological approaches, it has been possible to identify functional properties that segregate with these two receptors. Moreover, receptor modifications and factors that can alter the receptor response have been identified. Most importantly, recent data reveal the existence of a family of auxiliary GABA(B) receptor subunits that assemble as tetramers with the C-terminal domain of GABA(B2) subunits and drastically alter pharmacology and kinetics of the receptor response. The data are most consistent with native GABA(B) receptors minimally forming dimeric assemblies of units composed of GABA(B1), GABA(B2), and a tetramer of auxiliary subunits. This represents a substantial departure from current structural concepts for GPCRs.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Division of Physiology > Molecular Neurobiology Synaptic Plasticity (Bettler)
UniBasel Contributors:Bettler, Bernhard
Item Type:Article, refereed
Article Subtype:Further Journal Contribution
Bibsysno:Link to catalogue
Publisher:Elsevier
Note:Publication type according to Uni Basel Research Database: Journal item
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Last Modified:25 Oct 2013 08:32
Deposited On:25 Oct 2013 08:32

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