The regulatory pathway of a rhodopsin-like G-protein-coupled receptor-mediated insecticide resistance in the mosquitoes, Culex quinquefasciatus

Understanding genes and their regulatory functions involved in insecticide resistance will be fundamental for designing novel strategies to control insect pests, especially the resistant ones. Previous studies have identified a rhodopsin-like G-protein-coupled receptor (GPCR) gene overexpressed in pyrethoid resistant mosquitoes of Culex quinquefasciatus. GPCRs are involved in the G-protein-coupled signal transduction system and regulate many essential physiology processes and functions through the regulation of protein kinase pathway. The current study characterizes the regulatory pathway of the rhodopsin-like GPCR in insecticide resistance of Culex mosquitoes using double-stranded RNA-mediated gene interference (RNAi) technique and transgenic lines of Drosophila melanogaster. The study shows that knockdown of the rhodopsin-like GPCR gene expression in resistant mosquitoes causes a significant reduction in the mosquitoes’ resistance to permethrin, suggesting the involvement of the rhodopsin-like GPCR in the development of pyrethroid resistance. Moreover, knockdown of the rhodopsin-like GPCR gene expression causes the decrease in the gene expression of two protein kinases and four cytochrome P450s, which have been previously suggested to be involved in permethrin resistance of mosquitoes. Characterization of the rhodopsin-like GPCR transgenic lines of D. melanogaster elucidates increases in the levels of tolerance to permethrin and in the expression of three P450 genes, which have been reported in response to pyrethroid resistance in D. melanogaster. Taken together, the study strongly illustrates the role of the rhodopsin-like GPCR in the regulation of protein kinase signaling pathways and cytochrome P450 gene expression that, in turn, involved in detoxification of insecticides and development of resistance in Cx. quinquefasciatus.