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High Value-added Application of a Renewable Bioresource As Acaricide: Investigation the Mechanism of Action of Scoparone Against

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Journal J Adv Res
Date 2022 May 16
PMID 35572395
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Abstract

Introduction: Investigation into the action mechanisms of plant secondary metabolites against pests is a vital strategy for the development of novel promising biopesticides. Scoparone (isolated from ), a renewable plant-derived bioresource, displays potent acaricidal activities against mites, but its targets of action remain unclear.

Objectives: This study aimed to systematically explore the potential molecular targets of scoparone against and provide insights to guide the future application of scoparone as an agent for the management of agricultural mite pests worldwide.

Methods: The mechanism and potential targets of scoparone against mites were investigated using RNA-seq analysis; RNA interference (RNAi) assays; bioassays; and [Ca]i, pull-down and electrophysiological recording assays.

Results: RNA-seq analysis identified Ca signalling pathway genes, specifically 5 calmodulin (CaM1-5) genes and 1 each of L-, T-, N-type voltage-gated Ca channel (VGCC) genes, as candidate target genes for scoparone against mites. Furthermore, RNAi and electrophysiological data showed that the CaM1- and L-VGCC-mediated Ca signalling pathways were activated by scoparone. Interestingly, by promoting the interaction between CaM1 and the IQ motif (a consensus CaM-binding domain of L-VGCC), CaM1 markedly enhanced the activating effect of scoparone on L-VGCC. Pull-down assays further demonstrated that CaM interacted with the IQ motif, triggering L-VGCC opening. Importantly, mutation of the IQ motif significantly weakened CaM1 binding and eliminated the CaM1-mediated enhancement of scoparone-induced L-VGCC activation, indicating that the effect of scoparone was dependent on the CaM1-IQ interaction.

Conclusion: This study demonstrates, for the first time, that the acaricidal compound scoparone targets the interface between CaM1 and L-VGCC and activates the CaM-binding site, located in the IQ motif at the L-VGCC C-terminus. This work may contribute to the development of target-specific green acaricidal compounds based on L-VGCC.

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