A point mutation in a Drosophila GABA receptor confers insecticide resistance

@article{ffrenchConstant1993APM,
  title={A point mutation in a Drosophila GABA receptor confers insecticide resistance},
  author={Richard H. ffrench-Constant and Thomas A. Rocheleau and J. C. Steichen and Alison E. Chalmers},
  journal={Nature},
  year={1993},
  volume={363},
  pages={449-451}
}
VERTEBRATES and invertebrates both have GABA (γ-aminobutyric acid) as a major inhibitory neurotransmitter1,2. GABAA receptors in vertebrates assemble as heteromultimers to form an integral chloride ion channel3. These receptors are targets for drugs and pesticides4 and are also implicated in seizure-related diseases5,6. Picrotoxinin (PTX) and cyclodiene insecticides are GABAA receptor antagonists which competitively displace each other from the same binding site7. Insects8 and vertebrates9… 
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502 Citations

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Results suggest that target site insensitivity is associated with replacements at the first (A/G) but not the second (S/S′) locus, and may have arisen through a recent gene duplication event with respect to insecticide resistance and insect GABA receptor subunit diversity.
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Of the tested receptors, β-adrenergic-like octopamine receptors were revealed to be the most sensitive to the acaricide/insecticide amitraz, and ion channels and GPCRs remain potential targets for invertebrate pest control.
γ-Aminobutyrate- and Glutamate-gated Chloride Channels as Targets of Insecticides
Conservation of cyclodiene insecticide resistance‐associated mutations in insects
TLDR
The finding that precisely the same substitution is present in three pests from three different insect orders is reported, via the use of degenerate primers in the polymerase chain reaction, suggesting that there are a limited number of mutations that can confer resistance to cyclodienes, putative channel blockers, while still maintaining adequate chloride ion channel function.
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TLDR
This review focuses on the application of modern techniques in molecular biology, particularly mutational analysis, to identify structural domains of these receptors that are important for ligand recognition and receptor function.
Pleiotropic Effects of Loss of the Dα1 Subunit in Drosophila melanogaster: Implications for Insecticide Resistance
TLDR
This work used ends-out gene targeting to create a knockout of the Dα1 gene to facilitate phenotypic analysis in a controlled genetic background and reported the first report of a native function for any nAChR subunits known to be targeted by insecticides.
Ion channels as insecticide targets
TLDR
It is found that the insecticide-specific pharmacology of some receptors, like that containing subunits of the Rdl encoded GABA receptor, can be reconstituted with very few of the naturally occurring subunits expressed.
Chloride channels as tools for developing selective insecticides.
  • J. Bloomquist
  • Biology
    Archives of insect biochemistry and physiology
  • 2003
TLDR
The mode of action of the silphinenes, plant-derived natural compounds that structurally resemble picrotoxinin, are investigated, which antagonize the action of GABA on insect neurons and block GABA-mediated chloride uptake into mouse brain synaptoneurosomes in a noncompetitive manner.
Residues in the first transmembrane domain of the Caenorhabditis elegans GABAA receptor confer sensitivity to the neurosteroid pregnenolone sulfate
TLDR
Investigation of pregnenolone sulfate inhibition of the Caenorhabditis elegans UNC‐49 GABA receptor finds two regions required for PS inhibition, which may mediate neurosteroid action specifically, and not allosteric regulation in general.
The role of Rdl in resistance to phenylpyrazoles in Drosophila melanogaster.
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TLDR
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TLDR
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TLDR
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