Protein Gq modulates termination of phototransduction and prevents retinal degeneration
Department of Neurobiology
Medical Subject Headings
Alleles; Animals; Animals, Genetically Modified; Arrestins; Drosophila Proteins; Drosophila melanogaster; Electrophysiology; GTP-Binding Protein alpha Subunits, Gq-G11; Light; Light Signal Transduction; Models, Genetic; Mutation; Photoreceptor Cells, Invertebrate; Receptors, G-Protein-Coupled; Retinal Degeneration; Rhodopsin
Biochemistry, Biophysics, and Structural Biology | Neuroscience and Neurobiology
Appropriate termination of the phototransduction cascade is critical for photoreceptors to achieve high temporal resolution and to prevent excessive Ca(2+)-induced cell toxicity. Using a genetic screen to identify defective photoresponse mutants in Drosophila, we isolated and identified a novel Galpha(q) mutant allele, which has defects in both activation and deactivation. We revealed that G(q) modulates the termination of the light response and that metarhodopsin/G(q) interaction affects subsequent arrestin-rhodopsin (Arr2-Rh1) binding, which mediates the deactivation of metarhodopsin. We further showed that the Galpha(q) mutant undergoes light-dependent retinal degeneration, which is due to the slow accumulation of stable Arr2-Rh1 complexes. Our study revealed the roles of G(q) in mediating photoresponse termination and in preventing retinal degeneration. This pathway may represent a general rapid feedback regulation of G protein-coupled receptor signaling.
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Citation: J Biol Chem. 2012 Apr 20;287(17):13911-8. doi: 10.1074/jbc.M112.339895. Link to article on publisher's site