The G-protein-coupled receptor/PKA signaling pathway in insecticide resistance in the mosquito, Culex quinquefasciatus

G-protein-coupled receptors (GPCRs) are involved in signal transmission, which play pivotal physiological roles in insects, and have been proposed as a regulatory factor in mosquito insecticide resistance. Characterizing GPCRs and their regulatory pathway in insecticide resistance is fundamental for understanding the development of insecticide resistance in mosquito. Our current study has found that the expression pattern of a GPCR gene was significantly overexpressed in resistant mosquitoes and this overexpression was increased in mosquitoes following permethrin selection. Functional study through double-stranded RNA-mediated interference (RNAi) revealed that knockdown of GPCR gene in resistant mosquitoes resulted in increased susceptibility to permethrin, simultaneously causing the decreased gene expression of a protein kinase A gene (PKA, the downstream effector of GPCR pathways) and 4 resistance-related cytochrome P450 genes. The involvement of the PKA gene in permethrin resistance through the GPCR regulatory pathway by regulation of P450 gene expression was further characterized. Our study suggested an important role of the GPCR/PKA-mediated regulatory pathway governing P450 gene expression and P450-mediated resistance in Culex mosquitoes.