LsS6K acts as a negative regulator of thiamethoxam tolerance in Laodelphax striatellus.

The ribosomal protein S6 kinase (S6K) transduces the anabolic signals from nutrients and is involved in insect development and reproduction, however, its role in the regulation of the insecticide detoxification is still unclear. In this study, LsS6K was cloned and characterized from Laodelphax striatellus. RT-qPCR analysis revealed tissue-specific expression of LsS6K with the highest expression level in the fat body, and thiamethoxam exposure significantly down-regulated the expression of LsS6K at both the mRNA and protein levels. Functional analysis using RNA interference (RNAi) showed that knockdown of LsS6K significantly increased the tolerance of L. striatellus nymphs to thiamethoxam with concomitant upregulation of activity of cytochrome P450 monooxygenases (CYPs). Comparative transcriptome analysis identified six up-regulated P450 genes in dsLsS6K-injected nymphs compared with dsEGFP-injected nymphs, among which LsCYP4DE1 and LsCYP4C1 showed significant upregulation upon exposure to thiamethoxam. Further RNAi revealed that knockdown of LsCYP4DE1 and LsCYP4C1 significantly decreased the tolerance of nymphs to thiamethoxam. These results suggest that LsS6K is a negative regulator of thiamethoxam tolerance, and provide valuable insight into the cross-talk between nutrient signaling pathways and the detoxification regulatory network.