Résumé
The GABA
B receptor was the first heteromeric G-protein coupled receptor (GPCR) identified. Indeed, both GABA
B1 and GABA
B2 subunits appear necessary to get a functional GABA
B receptor. Soon after the cloning of both subunits, it was demonstrated that GABA
B2 was required for GABA
B1 to reach the cell surface. However, even a mutated GABA
B1 able to reach the cell surface is not functional alone despite its ability to bind GABA
B ligands. This clearly demonstrated that GABA
B2 is not only required for the correct trafficking of GABA
B1 but also for the correct functioning of the receptor. In the present review article, we will summarize our actual knowledge of the specific role of each subunit in ligand recognition, intramolecular transduction, G-protein activation and allosteric modulation. We will show that the GABA
B receptor is an heterodimer (not an hetero-oligomer), that agonists bind in GABA
B1, whereas GABA
B2 controls agonist affinity and is responsible for G-protein coupling. Finally, we will show that the recently identified positive allosteric modulator CGP7930 acts as a direct activator of the heptahelical domain of GABA
B2, being therefore the first GABA
B2 ligand identified so far.