Mutations M918T, M918L, and L1014F impair pyrethroid binding and alter gating of the Megalurothrips usitatus sodium channel
Abstract
Background: Mutations M918T/L and L1014F in the voltage-gated sodium channel (VGSC) are major causes of pyrethroid resistance in insects, but their functional effects in thrips remain unclear. We used Megalurothrips usitatus sodium channel (MuNav1-1) expression system to determine how these mutations affect channel gating and pyrethroid sensitivity.
Results: Electrophysiological analysis revealed that mutations shifted the voltage dependence of activation and inactivation. Notably, the L1014F mutation shifted the voltage dependence of activation by 8.32 mV in the depolarizing direction compared with wild-type MuNav1-1, whereas M918L resulted in a hyperpolarizing shift of 3.15 mV. Similarly, compared with wild-type MuNav1-1, L1014F and the double mutant M918T/L1014F shifted the voltage dependence of fast inactivation in the depolarizing direction by 5.52 and 6.23 mV, respectively. All mutants drastically reduced channel sensitivity to bifenthrin, permethrin, deltamethrin, and λ-cyhalothrin. The M918L mutant showed the greatest reduction in sensitivity (up to 40-fold), whereas the double mutant exhibited a strong synergistic resistance effect. Computational modeling indicated that the mutation directly impairs the binding affinity through the loss of hydrophobic contacts, with M918T severely disrupting hydrophobic interactions and L1014F inducing steric hindrance.
Conclusion: This study provides direct evidence that M918T/L and L1014F mediate pyrethroid resistance in M.…
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