Dataset Information

Regulation of P450-mediated permethrin resistance in Culex quinquefasciatus by the GPCR/G?s/AC/cAMP/PKA signaling cascade.

ABSTRACT: This study explores the role of G-protein-coupled receptor-intracellular signaling in the development of P450-mediated insecticide resistance in mosquitoes, Culex quinquefasciatus, focusing on the essential function of the GPCRs and their downstream effectors of Gs alpha subunit protein (G?s) and adenylyl cyclase (ACs) in P450-mediated insecticide resistance of Culex mosquitoes. Our RNAi-mediated functional study showed that knockdown of G?s caused the decreased expression of the downstream effectors of ACs and PKAs in the GPCR signaling pathway and resistance P450 genes, whereas knockdown of ACs decreased the expression of PKAs and resistance P450 genes. Knockdown of either G?s or ACs resulted in an increased susceptibility of mosquitoes to permethrin. These results add significantly to our understanding of the molecular basis of resistance P450 gene regulation through GPCR/G?s/AC/cAMP-PKA signaling pathways in the insecticide resistance of mosquitoes. The temporal and spatial dynamic analyses of GPCRs, G?s, ACs, PKAs, and P450s in two insecticide resistant mosquito strains revealed that all the GPCR signaling pathway components tested, namely GPCRs, G?s, ACs and PKAs, were most highly expressed in the brain for both resistant strains, suggesting the role played by these genes in signaling transduction and regulation. The resistance P450 genes were mainly expressed in the brain, midgut and malpighian tubules (MTs), suggesting their critical function in the central nervous system and importance for detoxification. The temporal dynamics analysis for the gene expression showed a diverse expression profile during mosquito development, indicating their initially functional importance in response to exposure to insecticides during their life stages.

SUBMITTER: Li T

PROVIDER: S-EPMC5613228 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Regulation of P450-mediated permethrin resistance in Culex quinquefasciatus by the GPCR/Gαs/AC/cAMP/PKA signaling cascade.

Li Ting T Liu Nannan N

Biochemistry and biophysics reports 20170819

This study explores the role of G-protein-coupled receptor-intracellular signaling in the development of P450-mediated insecticide resistance in mosquitoes, Culex quinquefasciatus, focusing on the essential function of the GPCRs and their downstream effectors of Gs alpha subunit protein (Gαs) and adenylyl cyclase (ACs) in P450-mediated insecticide resistance of Culex mosquitoes. Our RNAi-mediated functional study showed that knockdown of Gαs caused the decreased expression of the d ...[more]

PMID: 28955787

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Project description:To gain valuable insights into the gene interaction and the complex regulation system involved in the development of insecticide resistance in mosquitoes Culex quinquefasciatus, we conducted a whole transcriptome analysis of Culex mosquitoes following permethrin selection. Gene expression profiles for the lower resistant parental mosquito strain HAmCq(G0) and their permethrin-selected high resistant offspring HAmCq(G8) were compared and a total of 367 and 3982 genes were found to be up- and down-regulated, respectively, in HAmCq(G8), indicating that multiple genes are involved in response to permethrin selection. However, a similar overall cumulative gene expression abundance was identified between up- and down-regulated genes in HAmCq(G8) mosquitoes following permethrin selection, suggesting a homeostatic response to insecticides through a balancing of the up- and down-regulation of the genes. While structural and/or cuticular structural functions were the only two enriched GO terms for down-regulated genes, the enriched GO terms obtained for the up-regulated genes occurred primarily among the catalytic and metabolic functions where they represented three functional categories: electron carrier activity, binding, and catalytic activity. Interestingly, the functional GO terms in these three functional categories were overwhelmingly overrepresented in P450s and proteases/serine proteases. The important role played by P450s in the development of insecticide resistance has been extensively studied but the function of proteases/serine proteases in resistance is less well understood. Hence, the characterization of the functions of these proteins, including their digestive, catalytic and proteinase activities; regulation of signaling transduction and protein trafficking, immunity and storage; and their precise function in the development of insecticide resistance in mosquitoes will provide new insights into how genes are interconnected and regulated in resistance.

Dataset Information

Regulation of P450-mediated permethrin resistance in Culex quinquefasciatus by the GPCR/G?s/AC/cAMP/PKA signaling cascade.

Publications

Regulation of P450-mediated permethrin resistance in <i>Culex quinquefasciatus</i> by the GPCR/Gαs/AC/cAMP/PKA signaling cascade.

Similar Datasets

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