GABA(B) receptor subunit 1 binds to proteins affected in 22q11 deletion syndrome

Biochem Biophys Res Commun. 2010 Mar 5;393(2):185-9. doi: 10.1016/j.bbrc.2009.12.120. Epub 2009 Dec 28.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • DiGeorge Syndrome / genetics
  • DiGeorge Syndrome / metabolism*
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Neurons / metabolism
  • Nuclear Proteins
  • Protein Structure, Tertiary
  • Receptors, GABA-B / genetics
  • Receptors, GABA-B / metabolism*
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • DGCR6 protein, human
  • Extracellular Matrix Proteins
  • Nuclear Proteins
  • Receptors, GABA-B