In the mammalian central nervous system, slow inhibitory neurotransmission is largely mediated by metabotropic GABAB receptors (where GABA stands for γ-aminobutyric acid), which belong to the G-protein-coupled receptor gene family. Functional GABAB receptors are assembled from two subunits GABAB(1) (GABAB receptor subtype 1) and GABAB(2). For the GABAB(1) subunit, which binds the neurotransmitter GABA, two variants GABAB(1a) (GABAB receptor subtype 1 variant a) and GABAB(1b) 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 GABAB(1) 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 GABAB(2). 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 GABAB(1b) 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 GABAB(1) can be used for further functional or structural investigations.

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