GABAB receptor subunit 1 binds to proteins affected in 22q11 deletion syndrome

GABA_B receptors mediate slow inhibitory effects of the neurotransmitter γ-aminobutyric acid (GABA) on synaptic transmission in the central nervous system. They function as heterodimeric G-protein-coupled receptors composed of the seven-transmembrane domain proteins GABA_B1 and GABA_B2, which are linked through a coiled-coil interaction. The ligand-binding subunit GABA_B1 is at first retained in the endoplasmic reticulum and is transported to the cell surface only upon assembly with GABA_B2. Here, we report that GABA_B1, via the coiled-coil domain, can also bind to soluble proteins of unknown function, that are affected in 22q11 deletion/DiGeorge syndrome and are therefore referred to as DiGeorge critical region 6 (DGCR6). In transfected neurons the GABA_B1-DGCR6 association resulted in a redistribution of both proteins into intracellular clusters. Furthermore, the C-terminus of GABA_B2 interfered with the novel interaction, consistent with heterodimer formation overriding transient DGCR6-binding to GABA_B1. Thus, sequential coiled-coil interactions may direct GABA_B1 into functional receptors.