GABA(B) receptor subunit 1 binds to proteins affected in 22q11 deletion syndrome.
GABA(B) receptors mediate slow inhibitory effects of the neurotransmitter gamma-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.
Zunner
Dagmar
D
Center for Molecular Neurobiology, University of Hamburg, Germany.
Deschermeier
Christina
C
Kornau
Hans-Christian
HC
D000595:Amino Acid Sequence; D000818:Animals; D004062:DiGeorge Syndrome / Q000235:genetics / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D018080:Receptors, GABA-B / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D020798:Two-Hybrid System Techniques
C101273:DGCR6 protein, human; D016326:Extracellular Matrix Proteins; D009687:Nuclear Proteins; D018080:Receptors, GABA-B