A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a

Niraj S. Bende, Sławomir Dziemborowicz, Mehdi Mobli, Volker Herzig, John Gilchrist, Jordan Wagner, Graham M. Nicholson, Glenn F. King () and Frank Bosmans ()
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Niraj S. Bende: Institute for Molecular Bioscience, The University of Queensland
Sławomir Dziemborowicz: School of Medical and Molecular Biosciences, University of Technology
Mehdi Mobli: Centre for Advanced Imaging, The University of Queensland
Volker Herzig: Institute for Molecular Bioscience, The University of Queensland
John Gilchrist: School of Medicine, Johns Hopkins University
Jordan Wagner: School of Medicine, Johns Hopkins University
Graham M. Nicholson: School of Medical and Molecular Biosciences, University of Technology
Glenn F. King: Institute for Molecular Bioscience, The University of Queensland
Frank Bosmans: School of Medicine, Johns Hopkins University

Nature Communications, 2014, vol. 5, issue 1, 1-10

Abstract: Abstract β-Diguetoxin-Dc1a (Dc1a) is a toxin from the desert bush spider Diguetia canities that incapacitates insects at concentrations that are non-toxic to mammals. Dc1a promotes opening of German cockroach voltage-gated sodium (Nav) channels (BgNav1), whereas human Nav channels are insensitive. Here, by transplanting commonly targeted S3b–S4 paddle motifs within BgNav1 voltage sensors into Kv2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNav1 resistance to Dc1a, we identified two residues within the BgNav1 domain II S1–S2 loop that when mutated to their PaNav1 counterparts drastically reduce toxin susceptibility. Overall, our results reveal a distinct region within insect Nav channels that helps determine Dc1a sensitivity, a concept that will be valuable for the design of insect-selective insecticides.

Date: 2014
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DOI: 10.1038/ncomms5350

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