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Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits

Schwenk, Jochen and Metz, Michaela and Zolles, Gerd and Turecek, Rostislav and Fritzius, Thorsten and Bildl, Wolfgang and Tarusawa, Etsuko and Kulik, Akos and Unger, Andreas and Ivankova, Klara and Seddik, Riad and Tiao, Jim Y. and Rajalu, Mathieu and Trojanova, Johana and Rohde, Volker and Gassmann, Martin and Schulte, Uwe and Fakler, Bernd and Bettler, Bernhard. (2010) Native GABA(B) receptors are heteromultimers with a family of auxiliary subunits. Nature, Vol. 465, H. 7295. pp. 231-235.

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Official URL: http://edoc.unibas.ch/dok/A6004237

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Abstract

GABA(B) receptors are the G-protein-coupled receptors for gamma-aminobutyric acid (GABA), the main inhibitory neurotransmitter in the brain. They are expressed in almost all neurons of the brain, where they regulate synaptic transmission and signal propagation by controlling the activity of voltage-gated calcium (Ca(v)) and inward-rectifier potassium (K(ir)) channels. Molecular cloning revealed that functional GABA(B) receptors are formed by the heteromeric assembly of GABA(B1) with GABA(B2) subunits. However, cloned GABA(B(1,2)) receptors failed to reproduce the functional diversity observed with native GABA(B) receptors. Here we show by functional proteomics that GABA(B) receptors in the brain are high-molecular-mass complexes of GABA(B1), GABA(B2) and members of a subfamily of the KCTD (potassium channel tetramerization domain-containing) proteins. KCTD proteins 8, 12, 12b and 16 show distinct expression profiles in the brain and associate tightly with the carboxy terminus of GABA(B2) as tetramers. This co-assembly changes the properties of the GABA(B(1,2)) core receptor: the KCTD proteins increase agonist potency and markedly alter the G-protein signalling of the receptors by accelerating onset and promoting desensitization in a KCTD-subtype-specific manner. Taken together, our results establish the KCTD proteins as auxiliary subunits of GABA(B) receptors that determine the pharmacology and kinetics of the receptor response.
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:Research Article
Bibsysno:Link to catalogue
Publisher:Macmillan
ISSN:0028-0836
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Nov 2012 16:23
Deposited On:08 Nov 2012 16:18

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