A Single Residue Mutation in the Gα(q) Subunit of the G Protein Complex Causes Blindness in Drosophila.
A Single Residue Mutation in the Gα(q) Subunit of the G Protein Complex Causes Blindness in Drosophila.
复制标题
G 蛋白复合物 G α(q) 亚基中的单残基突变导致果蝇失明
DOI：
10.1534/g3.117.300340
复制
发表时间：
2018-01-04
期刊：
影响因子：
--
通讯作者：
Hu W
中科院分区：
文献类型：
--
作者：
Cao J;Bollepalli MK;Hu Y;Zhang J;Li Q;Li H;Chang H;Xiao F;Hardie RC;Rong YS;Hu W
异三聚体 G 蛋白在许多信号通路中发挥着核心作用，包括动物的光转导级联。然而，G 蛋白亚基 Gαq 的参与程度尚不清楚，因为先前报道的具有强烈功能丧失突变的动物仍然对光刺激有反应。我们在果蝇中发现了一个新的 Gαq 等位基因，它消除了传统视网膜电图测定中的光响应，并将分离细胞的全细胞记录的灵敏度降低了至少五个数量级。此外，突变的眼睛在光的存在下表现出快速的退化速度。我们的新等位基因可能是迄今为止描述的最强的亚型。有趣的是，突变蛋白是在眼睛中产生的，但携带保守疏水残基的单个氨基酸变化，该残基已被分配到 Gαq 及其下游效应器 PLC 之间的相互作用界面。因此，我们的研究可能发现了第一个专门影响体内这种相互作用的点突变。
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.