Cloning, Expression, and Gene Structure of a G Protein-Coupled Glutamate Receptor from Rat Brain

A complementary DNA encoding a G protein-coupled glutamate receptor from rat brain, Glu$_G$R, was cloned by functional expression in Xenopus oocytes. The complementary DNA encodes a protein of 1199 amino acids containing a seven-transmembrane motif, flanked by large amino- and carboxyl-terminal domains. This receptor lacks any amino acid sequence similarity with other G protein-coupled receptors, suggesting that it may be a member of a new subfamily. The presence of two introns flanking the central core suggests that Glu$_G$R may have evolved by exon shuffling. Expressed in oocytes, Glu$_G$R is activated by quisqualate > glutamate > ibotenate > trans-1-aminocyclopentyl-1,3-dicarboxylate, and it is inhibited by 2-amino-3-phosphonopropionate. Activation is blocked by Bordella pertussis toxin. These properties are typical of some metabotropic glutamate receptors.