Identification of a GABAB Receptor Subunit, gb2, Required for Functional GABAB Receptor Activity

• Published in: The Journal of biological chemistry Vol. 274; no. 12; pp. 7607 - 7610
• Main Authors: Ng, G Y, Clark, J, Coulombe, N, Ethier, N, Hebert, T E, Sullivan, R, Kargman, S, Chateauneuf, A, Tsukamoto, N, McDonald, T, Whiting, P, Mezey, E, Johnson, M P, Liu, Q, Kolakowski, Jr, L F, Evans, J F, Bonner, T I, O'Neill, G P
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 19-03-1999
• Subjects: Amino Acid Sequence; Animals; Azides - metabolism; COS Cells; Dimerization; G Protein-Coupled Inwardly-Rectifying Potassium Channels; Humans; In Situ Hybridization; Mice; Molecular Sequence Data; Organophosphorus Compounds - metabolism; Potassium Channels - metabolism; Potassium Channels, Inwardly Rectifying; Protein Conformation; Rats; Receptors, GABA-B - genetics; Receptors, GABA-B - metabolism; RNA, Messenger - metabolism; Structure-Activity Relationship; Xenopus laevis
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.274.12.7607

G protein-coupled receptors are commonly thought to bind their cognate ligands and elicit functional responses primarily as
monomeric receptors. In studying the recombinant γ-aminobutyric acid, type B (GABA B ) receptor (gb1a) and a GABA B -like orphan receptor (gb2), we observed that both receptors are functionally inactive when expressed individually in multiple
heterologous systems. Characterization of the tissue distribution of each of the receptors by in situ hybridization histochemistry in rat brain revealed co-localization of gb1 and gb2 transcripts in many brain regions, suggesting
the hypothesis that gb1 and gb2 may interact in vivo . In three established functional systems (inwardly rectifying K + channel currents in Xenopus oocytes, melanophore pigment aggregation, and direct cAMP measurements in HEK-293 cells), GABA mediated a functional response
in cells coexpressing gb1a and gb2 but not in cells expressing either receptor individually. This GABA activity could be blocked
with the GABA B receptor antagonist CGP71872. In COS-7 cells coexpressing gb1a and gb2 receptors, co-immunoprecipitation of gb1a and gb2
receptors was demonstrated, indicating that gb1a and gb2 act as subunits in the formation of a functional GABA B receptor.