title: Molecular basis of the remarkable species selectivity of an insecticidal sodium channel toxin from the African spider Augacephalus ezendami.
abstract: The inexorable decline in the armament of registered chemical insecticides has stimulated research into environmentally-friendly alternatives. Insecticidal spider-venom peptides are promising candidates for bioinsecticide development but it is challenging to find peptides that are specific for targeted pests. In the present study, we isolated an insecticidal peptide (Ae1a) from venom of the African spider Augacephalus ezendami (family Theraphosidae). Injection of Ae1a into sheep blowflies (Lucilia cuprina) induced rapid but reversible paralysis. In striking contrast, Ae1a was lethal to closely related fruit flies (Drosophila melanogaster) but induced no adverse effects in the recalcitrant lepidopteran pest Helicoverpa armigera. Electrophysiological experiments revealed that Ae1a potently inhibits the voltage-gated sodium channel BgNaV1 from the German cockroach Blattella germanica by shifting the threshold for channel activation to more depolarized potentials. In contrast, Ae1a failed to significantly affect sodium currents in dorsal unpaired median neurons from the American cockroach Periplaneta americana. We show that Ae1a interacts with the domain II voltage sensor and that sensitivity to the toxin is conferred by natural sequence variations in the S1-S2 loop of domain II. The phyletic specificity of Ae1a provides crucial information for development of sodium channel insecticides that target key insect pests without harming beneficial species.
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Volker
authors.initials: V
authors.lastname: Herzig
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Maria
authors.initials: M
authors.lastname: Ikonomopoulou
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: Smith
authors.affiliation: School of Medical &Molecular Biosciences, University of Technology, Sydney, NSW 2007, Australia.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Dziemborowicz
authors.affiliation: Department of Physiology &Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
authors.forename: John
authors.initials: J
authors.lastname: Gilchrist
authors.affiliation: Institute of Ecology &Evolution, University of Bern, CH 3012 Bern, Switzerland.
authors.forename: Lucia
authors.initials: L
authors.lastname: Kuhn-Nentwig
authors.affiliation: FIOCRUZ/Centro de Pesquisas René Rachou, Belo Horizonte, CEP 30190-002, MG, Brazil.
authors.forename: Fernanda Oliveira
authors.initials: FO
authors.lastname: Rezende
authors.affiliation: FIOCRUZ/Centro de Pesquisas René Rachou, Belo Horizonte, CEP 30190-002, MG, Brazil.
authors.forename: Luciano Andrade
authors.initials: LA
authors.lastname: Moreira
authors.affiliation: School of Medical &Molecular Biosciences, University of Technology, Sydney, NSW 2007, Australia.
authors.forename: Graham M
authors.initials: GM
authors.lastname: Nicholson
authors.affiliation: Department of Physiology &Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Bosmans
authors.affiliation: Institute for Molecular Bioscience, The University of Queensland, St. Lucia, QLD 4072, Australia.
authors.forename: Glenn F
authors.initials: GF
authors.lastname: King
mesh_terms: D000818:Animals; D020048:Blattellidae / Q000187:drug effects; D004175:Diptera / Q000187:drug effects; D004331:Drosophila melanogaster / Q000187:drug effects; D004353:Drug Evaluation, Preclinical / Q000379:methods; D019476:Insect Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D007306:Insecticides / Q000737:chemistry / Q000494:pharmacology*; D007915:Lepidoptera / Q000187:drug effects; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D010526:Periplaneta / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D013111:Spider Venoms / Q000737:chemistry*; D013112:Spiders / Q000737:chemistry / Q000502:physiology*; D061567:Voltage-Gated Sodium Channel Blockers / Q000494:pharmacology; D061566:Voltage-Gated Sodium Channels / Q000737:chemistry* / Q000378:metabolism
chemical_list: D019476:Insect Proteins; D007306:Insecticides; D062554:NAV1.5 Voltage-Gated Sodium Channel; D010455:Peptides; D011994:Recombinant Proteins; C568320:SCN5A protein, human; D013111:Spider Venoms; D061567:Voltage-Gated Sodium Channel Blockers; D061566:Voltage-Gated Sodium Channels