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

Bende, NS; Dziemborowicz, S; Mobli, M; Herzig, V; Gilchrist, J; Wagner, J; Nicholson, GM; King, GF; Bosmans, F

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

Bende, NS Dziemborowicz, S Mobli, M Herzig, V Gilchrist, J Wagner, J Nicholson, GM

King, GF Bosmans, F

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Publication Type:: Journal Article
Citation:: Nature Communications, 2014, 5
Issue Date:: 2014-07-11

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Field	Value	Language
dc.contributor.author	Bende, NS	en_US
dc.contributor.author	Dziemborowicz, S	en_US
dc.contributor.author	Mobli, M	en_US
dc.contributor.author	Herzig, V	en_US
dc.contributor.author	Gilchrist, J	en_US
dc.contributor.author	Wagner, J	en_US
dc.contributor.author	Nicholson, GM https://orcid.org/0000-0002-4277-4296	en_US
dc.contributor.author	King, GF	en_US
dc.contributor.author	Bosmans, F	en_US
dc.date.available	2014-06-10	en_US
dc.date.issued	2014-07-11	en_US
dc.identifier.citation	Nature Communications, 2014, 5	en_US
dc.identifier.uri	http://hdl.handle.net/10453/46215
dc.description.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 Na v channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv 2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav 1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNa v 1 resistance to Dc1a, we identified two residues within the BgNav 1 domain II S1-S2 loop that when mutated to their PaNav 1 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. © 2014 Macmillan Publishers Limited. All rights reserved.	en_US
dc.relation.ispartof	Nature Communications	en_US
dc.relation.isbasedon	10.1038/ncomms5350	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Spiders	en_US
dc.subject.mesh	Cockroaches	en_US
dc.subject.mesh	Spider Venoms	en_US
dc.subject.mesh	Insecticides	en_US
dc.subject.mesh	Species Specificity	en_US
dc.subject.mesh	Amino Acid Sequence	en_US
dc.subject.mesh	Molecular Sequence Data	en_US
dc.subject.mesh	Voltage-Gated Sodium Channels	en_US
dc.title	A distinct sodium channel voltage-sensor locus determines insect selectivity of the spider toxin Dc1a	en_US
dc.type	Journal Article
utslib.citation.volume	5	en_US
utslib.for	111506 Toxicology (incl. Clinical Toxicology)	en_US
utslib.for	030406 Proteins and Peptides	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - CHT - Health Technologies
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	closed_access
pubs.publication-status	Published	en_US
pubs.volume	5	en_US

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 Na v channels are insensitive. Here, by transplanting commonly targeted S3b-S4 paddle motifs within BgNav1 voltage sensors into Kv 2.1, we find that Dc1a interacts with the domain II voltage sensor. In contrast, Dc1a has little effect on sodium currents mediated by PaNav 1 channels from the American cockroach even though their domain II paddle motifs are identical. When exploring regions responsible for PaNa v 1 resistance to Dc1a, we identified two residues within the BgNav 1 domain II S1-S2 loop that when mutated to their PaNav 1 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. © 2014 Macmillan Publishers Limited. All rights reserved.

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http://hdl.handle.net/10453/46215