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Lookup NU author(s): Dr Susan Firbank
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In the mammalian central nervous system, slow inhibitory neurotransmission is largely mediated by metabotropic GABA(B) receptors (where GABA stands for gamma-aminobutyric acid), which belong to the G-protein-coupled receptor gene family. Functional GABA(B) receptors are assembled from two subunits GABA(B1) (GABA(B) receptor subtype 1) and GABA(B2). For the GABA(B1) subunit, which binds the neurotransmitter GABA, two variants GABA(B1a) (GABA(B) receptor subtype 1 variant a) and GABA(B1b) have been identified. They differ at the very N-terminus of their large glycosylated ECD (extracellular domain). To simplify the structural characterization, we designed truncated GABA(B1) receptors to identify the minimal functional domain which still binds a competitive radioligand and leads to a functional, GABA-responding receptor when co-expressed with GABA(B2). We show that it is necessary to include all the portion of the ECD encoded by exon 6 to exon 14. Furthermore, we studied mutant GABA(B1b) receptors, in which single or all potential N-glycosylation sites are removed. The absence of oligosaccharides does not impair receptor function, suggesting that the unglycosylated ECD of GABA(B1) can be used for further functional or structural investigations.
Author(s): Deriu D, Gassmann M, Firbank S, Ristig D, Lampert C, Mosbacher J, Froestl W, Kaupmann K, Bettler B, Grutter MG
Publication type: Article
Publication status: Published
Journal: Biochemical journal
Year: 2005
Volume: 386
Issue: 3
Pages: 423-431
ISSN (print): 0264-6021
ISSN (electronic): 1470-8728
Publisher: Portland Press Ltd.
URL: http://dx.doi.org/10.1042/BJ2004080
DOI: 10.1042/BJ20040804
Notes: Journal Article
Research Support, Non-U.S. Gov't
England
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