2. Academic Validation
  3. A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a

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

  • Nat Commun. 2014 Jul 11;5:4350. doi: 10.1038/ncomms5350.
Niraj S Bende 1,  Sławomir Dziemborowicz 2,  Mehdi Mobli 3,  Volker Herzig 1,  John Gilchrist 4,  Jordan Wagner 4,  Graham M Nicholson 2,  Glenn F King 1,  Frank Bosmans 5
Affiliations

Affiliations

  • 1 Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland QLD 4072, Australia.
  • 2 School of Medical and Molecular Biosciences, University of Technology, Sydney, New South Wales 2007, Australia.
  • 3 Centre for Advanced Imaging, The University of Queensland, St Lucia, Queensland QLD 4072, Australia.
  • 4 Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
  • 5 1] Department of Physiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA [2] Solomon H. Snyder Department of Neuroscience, School of Medicine, Johns Hopkins University, Baltimore, Maryland 21205, USA.
PMID: 25014760 DOI: 10.1038/ncomms5350
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.

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