A rhodopsin-like G-protein coupled receptor in insecticide resistance of mosquitoes, Culex quinquefasciatus

Understanding genes and their regulation function involved in mosquito resistance will be fundamental for designing novel strategies to control mosquitoes, especially the resistant ones. Our previous studies have identified a rhodopsin-like G-protein coupled receptor (GPCR) gene overexpressed in pyrethoid resistant mosquitoes of Culex quinquefasciatus. Rhodopsin-like GPCRs are involved in the G-protein-coupled signal transduction system and regulate many essential physiology processes and functions in insects. The current study investigated the expression of the rhodopsin-like GPCR gene in different mosquito populations, ranging from susceptible through intermediate to highly resistant ones. The rhodopsin-like GPCR gene was significantly overexpressed in resistant mosquitoes and the overexpression was increased in mosquitoes following permethrin selection. Furthermore, the expression of rhodopsin-like GPCR gene was up-regulated by permethrin insecticide treatment in highly resistant mosquitoes. Functional studies using double-stranded RNA-mediated gene interference (RNAi) technique revealed that knockdown of the rhodopsin-like GPCR gene in resistant mosquitoes caused a reduction of mosquitoes’ tolerance to permethrin and a decrease in the expression of several cytochrome P450 genes, which have been suggested to be involved in the detoxification of insecticides and development of resistance in mosquitoes. These results were further confirmed in the rhodopsin-like GPCR transgenic lines of Drosophila melanogaster, in which the tolerance to permethrin and the expression of P450 genes were increased. Taken together, these functional studies strongly revealed the role of the rhodopsin-like GPCR in the regulation of cytochrome P450 genes that, in turn, involved in detoxification of insecticides and evolution of resistance in Culex mosquitoes.