1. A Single Residue Mutation in the Gαq Subunit of the G Protein Complex Causes Blindness in Drosophila
- Author
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Jinguo Cao, Qiang Li, Murali K. Bollepalli, Hua Chang, Feng Xiao, Yikang S Rong, Hongmei Li, Jin Zhang, Wen Hu, Roger C. Hardie, Yuhui Hu, Rong, Yikang S [0000-0002-9787-9669], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Light ,G protein ,Protein subunit ,phototransduction ,Biology ,QH426-470 ,Investigations ,Retina ,03 medical and health sciences ,Mutant protein ,Heterotrimeric G protein ,Genetics ,Electroretinography ,Animals ,Drosophila Proteins ,Point Mutation ,Gαq ,Molecular Biology ,Genetics (clinical) ,Alleles ,Vision, Ocular ,Gα PLC interaction ,Point mutation ,Retinal Degeneration ,light-induced retinal degeneration ,Molecular biology ,photoreceptor ,G beta-gamma complex ,030104 developmental biology ,Drosophila melanogaster ,Gq alpha subunit ,Gene Expression Regulation ,ERG ,Type C Phospholipases ,biology.protein ,GTP-Binding Protein alpha Subunits, Gq-G11 ,Drosophila Protein ,Protein Binding - Abstract
Heterotrimeric G proteins play central roles in many signaling pathways, including the phototransduction cascade in animals. However, the degree of involvement of the G protein subunit Gαq is not clear since animals with previously reported strong loss-of-function mutations remain responsive to light stimuli. We recovered a new allele of Gαq in Drosophila that abolishes light response in a conventional electroretinogram assay, and reduces sensitivity in whole-cell recordings of dissociated cells by at least five orders of magnitude. In addition, mutant eyes demonstrate a rapid rate of degeneration in the presence of light. Our new allele is likely the strongest hypomorph described to date. Interestingly, the mutant protein is produced in the eyes but carries a single amino acid change of a conserved hydrophobic residue that has been assigned to the interface of interaction between Gαq and its downstream effector, PLC. Our study has thus uncovered possibly the first point mutation that specifically affects this interaction in vivo.
- Published
- 2017