RT Journal Article
SR Electronic
T1 Altered G-Protein Coupling in an mGluR6 Point Mutant Associated with Congenital Stationary Night Blindness
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 992
OP 997
DO 10.1124/mol.109.058628
VO 76
IS 5
A1 Donald Beqollari
A1 Matthew J. Betzenhauser
A1 Paul J. Kammermeier
YR 2009
UL http://molpharm.aspetjournals.org/content/76/5/992.abstract
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