title: Protein Gq modulates termination of phototransduction and prevents retinal degeneration.
abstract: 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 Gα(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 Gα(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.
authors.affiliation: Institute of Life Science, the Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Hu
authors.forename: Didi
authors.initials: D
authors.lastname: Wan
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Yu
authors.forename: Jinguo
authors.initials: J
authors.lastname: Cao
authors.forename: Peiyi
authors.initials: P
authors.lastname: Guo
authors.forename: Hong-Sheng
authors.initials: HS
authors.lastname: Li
authors.forename: Junhai
authors.initials: J
authors.lastname: Han
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D019390:Arrestins / Q000737:chemistry; D029721:Drosophila Proteins / Q000737:chemistry; D004331:Drosophila melanogaster / Q000235:genetics; D004594:Electrophysiology; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D008027:Light; D055537:Light Signal Transduction; D008957:Models, Genetic; D009154:Mutation; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry; D012162:Retinal Degeneration / Q000378:metabolism* / Q000517:prevention & control*; D012243:Rhodopsin / Q000737:chemistry / Q000378:metabolism
chemical_list: C504666:Arr2 protein, Drosophila; D019390:Arrestins; D029721:Drosophila Proteins; D043562:Receptors, G-Protein-Coupled; C013110:metarhodopsins; D012243:Rhodopsin; D043802:GTP-Binding Protein alpha Subunits, Gq-G11