Multiple sodium channel variants in the mosquito Culex quinquefasciatus.

Multiple sodium channel variants in the mosquito Culex quinquefasciatus.
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DOI:
10.7150/ijbs.4966
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发表时间:
2012
影响因子:
9.2
通讯作者:
Liu N
Liu N
中科院分区:
生物学2区
文献类型:
--
作者:
He L;Li T;Zhang L;Liu N

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电压门控钠通道是滴滴涕(DDT)和拟除虫菊酯类杀虫剂的作用靶点。可变剪接作为决定钠通道结构和功能多样性以及由此导致昆虫和螨类产生抗药性的关键机制,其重要性已得到广泛认可,大量针对医学和农业重要昆虫物种钠通道可变剪接及变体特征的研究便是例证。在此,我们首次对致倦库蚊钠通道转录本的多种变体进行了比较研究。根据区分性序列大小,这些变体分别归类为CxNa - L和CxNa - S两类,其序列大小分别约为6.5 kb和4.0 kb,在敏感的S - Lab品系、低抗性的HAmCqG0品系以及高抗性的HAmCqG8致倦库蚊品系中,通过主要的广泛可变剪接并伴随少量小的缺失/插入产生。我们鉴定出4种Cx - Na - L可变剪接变体,其中3种为全长变体,带有3个可选外显子(2、5和21i),另1种带有框内终止密码子。在CxNa - S类别中鉴定出大的多外显子可变剪接。S - Lab和HAmCqG0品系中的所有CxNa - S剪接变体都含有框内终止密码子,这表明由此产生的任何蛋白质都将被截断。与CxNa - L剪接变体相比,这些带有终止密码子的剪接变体的表达量低约1000至3000倍,这可能表明这些变体在S - Lab和HAmCqG0中的重要性较低。有趣的是,HAmCqG8品系中CxNa - S的两种可变剪接变体包含完整的开放阅读框(ORF),但缺失外显子5至18,且这两种变体在HAmCqG8中的表达水平远高于S - Lab和HAmCqG0。这些结果为进一步阐明电压门控钠通道的可变剪接如何促成蚊子神经元信号传导的多样性以响应拟除虫菊酯提供了功能基础,并且可能暗示了这些变体在拟除虫菊酯抗性发展中的作用。
Voltage-gated sodium channels are the target sites of both DDT and pyrethroid insecticides. The importance of alternative splicing as a key mechanism governing the structural and functional diversity of sodium channels and the resulting development of insecticide and acaricide resistance is widely recognized, as shown by the extensive research on characterizing alternative splicing and variants of sodium channels in medically and agriculturally important insect species. Here we present the first comparative study of multiple variants of the sodium channel transcripts in the mosquito Culex quinquefasciatus. The variants were classified into two categories, CxNa-L and CxNa-S based on their distinguishing sequence sizes of ~6.5 kb and ~4.0 kb, respectively, and generated via major extensive alternative splicing with minor small deletions/ insertions in susceptible S-Lab, low resistant HAmCqG0, and highly resistant HAmCqG8 Culex strains. Four alternative Cx-Na-L splice variants were identified, including three full length variants with three optional exons (2, 5, and 21i) and one with in-frame-stop codons. Large, multi-exon-alternative splices were identified in the CxNa-S category. All CxNa-S splicing variants in the S-Lab and HAmCqG0 strains contained in-frame stop codons, suggesting that any resulting proteins would be truncated. The ~1000 to ~3000-fold lower expression of these splice variants with stop codons compared with the CxNa-L splicing variants may support the lower importance of these variants in S-Lab and HAmCqG0. Interestingly, two alternative splicing variants of CxNa-S in HAmCqG8 included entire ORFs but lacked exons 5 to18 and these two variants had much higher expression levels in HAmCqG8 than in S-Lab and HAmCqG0. These results provide a functional basis for further characterizing how alternative splicing of a voltage-gated sodium channel contributes to diversity in neuronal signaling in mosquitoes in response to pyrethroids, and possibly indicates the role of these variants in the development of pyrethroid resistance.
DOI: 10.1038/srep00781
发表时间: 2012
期刊: SCIENTIFIC REPORTS
影响因子: 4.6
作者:
Li, Ting;Zhang, Lee;Reid, William R.;Xu, Qiang;Dong, Ke;Liu, Nannan
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发表时间: 2004-01-01
期刊: BIOTECHNIQUES
影响因子: 2.7
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发表时间: 2009-09-01
影响因子: 2.5
作者:
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DOI: 10.1126/science.1191864
发表时间: 2010-10-01
期刊: Science (New York, N.Y.)
影响因子: --
作者:
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通讯作者: Atkinson PW
DOI: 10.1073/pnas.91.7.2483
发表时间: 1994-03-29
影响因子: 11.1
作者:
KNIPPLE, DC;DOYLE, KE;SODERLUND, DM
通讯作者: SODERLUND, DM