Li Ting, Liu Nannan
Department of Entomology and Plant Pathology, Funchess Hall, Auburn University, Auburn, AL.
J Med Entomol. 2018 Jun 28;55(4):862-870. doi: 10.1093/jme/tjy022.
G-protein-coupled receptors (GPCRs) are a large family of seven-transmembrane domain proteins that exist in plants and animals, playing critical physiological functions through intracellular cascades. Previous studies revealed an important regulation pathway of GPCR/Guanine nucleotide-binding protein (G-protein)/Adenylyl Cyclase (AC)/cAMP-dependent protein kinase A (PKA) in the insecticide resistance and regulation of resistance-related P450 gene expression in highly resistant southern house mosquitoes, Culex quinquefasciatus Say (Diptera: Culicidae). However, the function of this regulation pathway in field-collected and laboratory-susceptible mosquitoes is still unknown. In the current study, we characterized the function of each effector (GPCR, G-protein, AC, and PKA) in this GPCR intracellular pathway in both field-collected and laboratory Cx. quinquefasciatus strains, showing that knockdown of the expression of each effector gene can cause 1) decreased expression of their downstream respective genes and 2) increased sensitivity of the mosquitoes to permethrin insecticide. These results, together with our previous findings, strongly suggest the universal function of the GPCR-regulation cascade in the mosquito's sensitivity to insecticides and its regulation of resistance development through P450-mediated detoxification.
G蛋白偶联受体（GPCRs）是一类存在于动植物中的具有七个跨膜结构域的蛋白大家族，通过细胞内级联反应发挥关键的生理功能。先前的研究揭示了一条重要的调控途径，即GPCR/鸟嘌呤核苷酸结合蛋白（G蛋白）/腺苷酸环化酶（AC）/环磷酸腺苷依赖性蛋白激酶A（PKA）途径，该途径在高抗性南方家蚊致倦库蚊（双翅目：蚊科）的抗药性及抗性相关P450基因表达调控中发挥作用。然而，这条调控途径在野外采集的以及实验室易感的蚊子中的功能仍不清楚。在本研究中，我们对这条GPCR细胞内途径中的每个效应器（GPCR、G蛋白、AC和PKA）在野外采集的和实验室的致倦库蚊品系中的功能进行了表征，结果表明，每个效应器基因表达的敲低可导致：1）其下游各自基因的表达降低；2）蚊子对氯菊酯杀虫剂的敏感性增加。这些结果与我们之前的发现共同有力地表明，GPCR调控级联在蚊子对杀虫剂的敏感性及其通过P450介导的解毒作用对抗性发展的调控中具有普遍功能。
