Altered G-protein coupling in an mGluR6 point mutant associated with congenital stationary night blindness.
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 G(o) coupling but retains coupling to G(i), which may explain the phenotype.
Beqollari
Donald
D
Department of Pharmacology and Physiology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Betzenhauser
Matthew J
MJ
Kammermeier
Paul J
PJ
D000818:Animals; D002460:Cell Line; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D009755:Night Blindness / Q000151:congenital / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D017354:Point Mutation / Q000502:physiology*; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000502:physiology
D018094:Receptors, Metabotropic Glutamate; C113897:metabotropic glutamate receptor 6; D019206:GTP-Binding Protein alpha Subunits, Gi-Go