Evidence map›Paper›PMID 25523031›Full record

ArticleMolecular pharmacology2015

A mutation in the intracellular loop III/IV of mosquito sodium channel synergizes the effect of mutations in helix IIS6 on pyrethroid resistance.

Lingxin Wang, Yoshiko Nomura, Yuzhe Du, Nannan Liu, Boris S Zhorov, Ke Dong

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 42 citations in OpenAlex.

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  15. Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities.Proceedings of the National Academy of Sciences of the United States of America · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 3 countries.

Lingxin WangDepartment of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, Michigan (L.W., Y.N., Y.D., K.D.); Department of Entomology and Plant Pathology; Auburn University, Auburn, Alabama (N.L.); Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada (B.S.Z.); and Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia (B.S.Z.).
Yoshiko NomuraDepartment of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, Michigan (L.W., Y.N., Y.D., K.D.); Department of Entomology and Plant Pathology; Auburn University, Auburn, Alabama (N.L.); Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada (B.S.Z.); and Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia (B.S.Z.).
Yuzhe DuDepartment of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, Michigan (L.W., Y.N., Y.D., K.D.); Department of Entomology and Plant Pathology; Auburn University, Auburn, Alabama (N.L.); Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada (B.S.Z.); and Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia (B.S.Z.).
Nannan LiuDepartment of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, Michigan (L.W., Y.N., Y.D., K.D.); Department of Entomology and Plant Pathology; Auburn University, Auburn, Alabama (N.L.); Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada (B.S.Z.); and Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia (B.S.Z.).
Boris S ZhorovDepartment of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, Michigan (L.W., Y.N., Y.D., K.D.); Department of Entomology and Plant Pathology; Auburn University, Auburn, Alabama (N.L.); Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada (B.S.Z.); and Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia (B.S.Z.).
Ke DongDepartment of Entomology, Genetics and Neuroscience Programs, Michigan State University, East Lansing, Michigan (L.W., Y.N., Y.D., K.D.); Department of Entomology and Plant Pathology; Auburn University, Auburn, Alabama (N.L.); Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada (B.S.Z.); and Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia (B.S.Z.) dongk@cns.msu.edu.
Auburn University · USMichigan State University · USMcMaster University · CA

Funding

Molecular mechanisms of action and resistance of sodium channel-targeting insectiR01GM057440 · NIGMS · MICHIGAN STATE UNIVERSITY · PI DONG, KE, HUGHSON, FREDERICK M · 1999 to 2023
$5.4M
Characterization of the sodium channel mutations involved in insecticide resistanR21AI090303 · NIAID · AUBURN UNIVERSITY AT AUBURN · PI LIU, NANNAN · 2010 to 2011
$408k
NIAID NIH HHS R21 AI090303NIAID NIH HHS R21-AI090303NIGMS NIH HHS R01 GM057440NIGMS NIH HHS R01-GM057440
6 · The paper itself

Abstract

Activation and inactivation of voltage-gated sodium channels are critical for proper electrical signaling in excitable cells. Pyrethroid insecticides promote activation and inhibit inactivation of sodium channels, resulting in prolonged opening of sodium channels. They preferably bind to the open state of the sodium channel by interacting with two distinct receptor sites, pyrethroid receptor sites PyR1 and PyR2, formed by the interfaces of domains II/III and I/II, respectively. Specific mutations in PyR1 or PyR2 confer pyrethroid resistance in various arthropod pests and disease vectors. Recently, a unique mutation, N(1575)Y, in the cytoplasmic loop linking domains III and IV (LIII/IV) was found to coexist with a PyR2 mutation, L(1014)F in IIS6, in pyrethroid-resistant populations of Anopheles gambiae. To examine the role of this mutation in pyrethroid resistance, N(1575)Y alone or N(1575)Y + L(1014)F were introduced into an Aedes aegypti sodium channel, AaNav1-1, and the mutants were functionally examined in Xenopus oocytes. N(1575)Y did not alter AaNav1-1 sensitivity to pyrethroids. However, the N(1575)Y + L(1014)F double mutant was more resistant to pyrethroids than the L(1014)F mutant channel. Further mutational analysis showed that N(1575)Y could also synergize the effect of L(1014)S/W, but not L(1014)G or other pyrethroid-resistant mutations in IS6 or IIS6. Computer modeling predicts that N(1575)Y allosterically alters PyR2 via a small shift of IIS6. Our findings provide the molecular basis for the coexistence of N(1575)Y with L(1014)F in pyrethroid resistance, and suggest an allosteric interaction between IIS6 and LIII/IV in the sodium channel.

Indexed as

AnimalsCulicidaeDrug ResistanceFemaleInsecticidesMembrane PotentialsMutationProtein Structure, SecondaryPyrethrinsSodium ChannelsXenopus laevisInsecticidesPyrethrinsSodium Channels

Identifiers

PMID25523031
PMCPMC4352587
OpenAlexW2333253878

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.