PT - JOURNAL ARTICLE AU - Donald Beqollari AU - Matthew J. Betzenhauser AU - Paul J. Kammermeier TI - Altered G-Protein Coupling in an mGluR6 Point Mutant Associated with Congenital Stationary Night Blindness AID - 10.1124/mol.109.058628 DP - 2009 Nov 01 TA - Molecular Pharmacology PG - 992--997 VI - 76 IP - 5 4099 - http://molpharm.aspetjournals.org/content/76/5/992.short 4100 - http://molpharm.aspetjournals.org/content/76/5/992.full SO - Mol Pharmacol2009 Nov 01; 76 AB - The highly specialized metabotropic glutamate receptor type 6 (mGluR6) is postsynaptically localized and expressed only in the dendrites of ON bipolar cells. Upon activation of mGluR6 by glutamate released from photoreceptors, a nonselective cation channel is inhibited, causing these cells to hyperpolarize. Mutations in this gene have been implicated in the development of congenital stationary night blindness type 1 (CSNB1). We investigated five known mGluR6 point mutants that lead to CSNB1 to determine the molecular mechanism of each phenotype. In agreement with other studies, four mutants demonstrated trafficking impairment. However, mGluR6 E775K (E781K in humans) suggested no trafficking or signaling deficiencies measured by our initial assays. Most importantly, our results indicate a switch in G-protein coupling, in which E775K loses Go coupling but retains coupling to Gi, which may explain the phenotype. © 2009 The American Society for Pharmacology and Experimental Therapeutics