These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Functional validation of A2'N mutation of the RDL GABA receptor against fipronil via molecular modeling and genome engineering in drosophila.
    Author: Qiao X, Zhou T, Zhang J, Zhang L, Lu Y, Huang J.
    Journal: Pest Manag Sci; 2024 Apr; 80(4):1924-1929. PubMed ID: 38086568.
    Abstract:
    BACKGROUND: Insect RDL (resistant to dieldrin) receptors are essential pentameric ligand-gated chloride channels that mediate the neuroinhibitory effect of GABA, the chief inhibitory neurotransmitter in the central nervous system. These receptors serve as primary targets for various insecticides, including noncompetitive antagonists (NCAs) such as cyclodiene organochlorines and phenylpyrazoles, as well as allosteric modulators like meta-diamides and isoxazolines. This study focuses on a newly discovered A2'N mutation within the RDL receptors, identified in fipronil-resistant planthoppers. Despite in vitro electrophysiological studies have proposed its role in conferring target-site resistance, in vivo genetic functional validation of this mutation remains unexplored. RESULTS: Our research employed toxicity bioassays, assessing various Rdl genotypes against a spectrum of insecticides, including fipronil, α-endosulfan, broflanilide, and isocycloseram. Results revealed distinct resistance profiles for A2'N and A2'S mutants, indicating different binding interactions of RDL receptors with NCAs. Significantly, the A2'N heterozygote showed substantial resistance to fipronil, despite its homozygous lethality. Molecular modeling and docking simulations further supported these findings, highlighting unique binding poses for fipronil and α-endosulfan. CONCLUSION: This study confirmed that A2'N mutation of the RDL GABA receptor confer high resistance to fipronil in vivo. The observed resistance in A2'N mutants is likely attributable to a steric hindrance mechanism, wherein the introduction of larger side chains hampers fipronil binding, even in a heterozygous state. © 2023 Society of Chemical Industry.
    [Abstract] [Full Text] [Related] [New Search]