Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Proc Natl Acad Sci U S A
2013 Jul 16;11029:11785-90. doi: 10.1073/pnas.1305118110.
Show Gene links
Show Anatomy links
Molecular evidence for dual pyrethroid-receptor sites on a mosquito sodium channel.
Du Y, Nomura Y, Satar G, Hu Z, Nauen R, He SY, Zhorov BS, Dong K.
???displayArticle.abstract???
Pyrethroid insecticides are widely used as one of the most effective control measures in the global fight against agricultural arthropod pests and mosquito-borne diseases, including malaria and dengue. They exert toxic effects by altering the function of voltage-gated sodium channels, which are essential for proper electrical signaling in the nervous system. A major threat to the sustained use of pyrethroids for vector control is the emergence of mosquito resistance to pyrethroids worldwide. Here, we report the successful expression of a sodium channel, AaNav1-1, from Aedes aegypti in Xenopus oocytes, and the functional examination of nine sodium channel mutations that are associated with pyrethroid resistance in various Ae. aegypti and Anopheles gambiae populations around the world. Our analysis shows that five of the nine mutations reduce AaNav1-1 sensitivity to pyrethroids. Computer modeling and further mutational analysis revealed a surprising finding: Although two of the five confirmed mutations map to a previously proposed pyrethroid-receptor site in the house fly sodium channel, the other three mutations are mapped to a second receptor site. Discovery of this second putative receptor site provides a dual-receptor paradigm that could explain much of the molecular mechanisms of pyrethroid action and resistance as well as the high selectivity of pyrethroids on insect vs. mammalian sodium channels. Results from this study could impact future prediction and monitoring of pyrethroid resistance in mosquitoes and other arthropod pests and disease vectors.
Bloomquist,
Ion channels as targets for insecticides.
1996, Pubmed
Bloomquist,
Ion channels as targets for insecticides.
1996,
Pubmed Butler,
Mosquitoes score in chemical war.
2011,
Pubmed Davies,
DDT, pyrethrins, pyrethroids and insect sodium channels.
2007,
Pubmed Du,
Batrachotoxin, pyrethroids, and BTG 502 share overlapping binding sites on insect sodium channels.
2011,
Pubmed Du,
Identification of a cluster of residues in transmembrane segment 6 of domain III of the cockroach sodium channel essential for the action of pyrethroid insecticides.
2009,
Pubmed Du,
A negative charge in transmembrane segment 1 of domain II of the cockroach sodium channel is critical for channel gating and action of pyrethroid insecticides.
2010,
Pubmed Du,
Identification of new batrachotoxin-sensing residues in segment IIIS6 of the sodium channel.
2011,
Pubmed
,
Xenbase Feng,
Cloning and functional analysis of TipE, a novel membrane protein that enhances Drosophila para sodium channel function.
1995,
Pubmed
,
Xenbase Garden,
Docking flexible ligands in proteins with a solvent exposure- and distance-dependent dielectric function.
2010,
Pubmed Jiang,
The open pore conformation of potassium channels.
2002,
Pubmed Jones,
Footprints of positive selection associated with a mutation (N1575Y) in the voltage-gated sodium channel of Anopheles gambiae.
2012,
Pubmed Li,
Monte Carlo-minimization approach to the multiple-minima problem in protein folding.
1987,
Pubmed Long,
Crystal structure of a mammalian voltage-dependent Shaker family K+ channel.
2005,
Pubmed Lund,
Dose-dependent interaction of the pyrethroid isomers with sodium channels of squid axon membranes.
1982,
Pubmed Narahashi,
Differential actions of insecticides on target sites: basis for selective toxicity.
2007,
Pubmed Narahashi,
Neuronal ion channels as the target sites of insecticides.
1996,
Pubmed O'Reilly,
Modelling insecticide-binding sites in the voltage-gated sodium channel.
2006,
Pubmed Payandeh,
The crystal structure of a voltage-gated sodium channel.
2011,
Pubmed Rinkevich,
Diversity and Convergence of Sodium Channel Mutations Involved in Resistance to Pyrethroids.
2013,
Pubmed Smith,
Action of the pyrethroid insecticide cypermethrin on rat brain IIa sodium channels expressed in xenopus oocytes.
1998,
Pubmed
,
Xenbase Soderlund,
State-Dependent Modification of Voltage-Gated Sodium Channels by Pyrethroids.
2010,
Pubmed
,
Xenbase Soderlund,
Molecular mechanisms of pyrethroid insecticide neurotoxicity: recent advances.
2012,
Pubmed Song,
RNA editing generates tissue-specific sodium channels with distinct gating properties.
2004,
Pubmed
,
Xenbase Tatebayashi,
Differential mechanism of action of the pyrethroid tetramethrin on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels.
1994,
Pubmed Tikhonov,
Architecture and pore block of eukaryotic voltage-gated sodium channels in view of NavAb bacterial sodium channel structure.
2012,
Pubmed Usherwood,
Mutations in DIIS5 and the DIIS4-S5 linker of Drosophila melanogaster sodium channel define binding domains for pyrethroids and DDT.
2007,
Pubmed
,
Xenbase Vais,
A single amino acid change makes a rat neuronal sodium channel highly sensitive to pyrethroid insecticides.
2000,
Pubmed
,
Xenbase Vais,
Activation of Drosophila sodium channels promotes modification by deltamethrin. Reductions in affinity caused by knock-down resistance mutations.
2000,
Pubmed
,
Xenbase Wang,
A phenylalanine residue at segment D3-S6 in Nav1.4 voltage-gated Na(+) channels is critical for pyrethroid action.
2001,
Pubmed Warmke,
Functional expression of Drosophila para sodium channels. Modulation by the membrane protein TipE and toxin pharmacology.
1997,
Pubmed
,
Xenbase Weiner,
An all atom force field for simulations of proteins and nucleic acids.
1986,
Pubmed Xu,
Evolutionary adaptation of the amino acid and codon usage of the mosquito sodium channel following insecticide selection in the field mosquitoes.
2012,
Pubmed Zhorov,
Potassium, sodium, calcium and glutamate-gated channels: pore architecture and ligand action.
2004,
Pubmed
