A Single Residue Mutation in the Gα q Subunit of the G Protein Complex Causes Blindness in Drosophila

• Published in: G3 : genes - genomes - genetics Vol. 8; no. 1; pp. 363 - 371
• Main Authors: Cao, Jinguo, Bollepalli, Murali K, Hu, Yuhui, Zhang, Jin, Li, Qiang, Li, Hongmei, Chang, Hua, Xiao, Feng, Hardie, Roger C, Rong, Yikang S, Hu, Wen
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01.01.2018; Oxford University Press
• Subjects: ERG; G protein; Gα PLC interaction; Gαq; Investigations; light-induced retinal degeneration; photoreceptor; phototransduction; Gα PLC interaction; light-induced retinal degeneration; Gαq; photoreceptor; ERG; phototransduction; G protein
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1534/g3.117.300340

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 Gα is not clear since animals with previously reported strong loss-of-function mutations remain responsive to light stimuli. We recovered a new allele of in 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 Gα and its downstream effector, PLC. Our study has thus uncovered possibly the first point mutation that specifically affects this interaction .