Jones Andrew K, Sattelle David B
MRC Functional Genetics Unit, Department of Physiology Anatomy and Genetics, The Sherrington Building, University of Oxford, South Parks Road, Oxford OX1 3QX, UK.
BMC Genomics. 2007 Sep 19;8:327. doi: 10.1186/1471-2164-8-327.
Members of the cys-loop ligand-gated ion channel (cys-loop LGIC) superfamily mediate chemical neurotransmission and are studied extensively as potential targets of drugs used to treat neurological disorders such as Alzheimer's disease. Insect cys-loop LGICs are also of interest as they are targets of highly successful insecticides. The red flour beetle, Tribolium castaneum, is a major pest of stored agricultural products and is also an important model organism for studying development.
As part of the T. castaneum genome sequencing effort, we have characterized the beetle cys-loop LGIC superfamily which is the third insect superfamily to be described after those of Drosophila melanogaster and Apis mellifera, and also the largest consisting of 24 genes. As with Drosophila and Apis, Tribolium possesses ion channels gated by acetylcholine, gamma-amino butyric acid (GABA), glutamate and histamine as well as orthologs of the Drosophila pH-sensitive chloride channel subunit (pHCl), CG8916 and CG12344. Similar to Drosophila and Apis, Tribolium cys-loop LGIC diversity is broadened by alternative splicing although the beetle orthologs of RDL and GluCl possess more variants of exon 3. Also, RNA A-to-I editing was observed in two Tribolium nicotinic acetylcholine receptor subunits, Tcasalpha6 and Tcasbeta1. Editing in Tcasalpha6 is evolutionarily conserved with D. melanogaster, A. mellifera and Heliothis virescens, whereas Tcasbeta1 is edited at a site so far only observed in the beetle.
Our findings reveal that in diverse insect species the cys-loop LGIC superfamily has remained compact with only minor changes in gene numbers. However, alternative splicing, RNA editing and the presence of divergent subunits broadens the cys-loop LGIC proteome and generates species-specific receptor isoforms. These findings on Tribolium castaneum enhance our understanding of cys-loop LGIC functional genomics and provide a useful basis for the development of improved insecticides that target an important agricultural pest.
半胱氨酸环配体门控离子通道（cys-loop LGIC）超家族的成员介导化学神经传递，并且作为用于治疗诸如阿尔茨海默病等神经疾病的药物的潜在靶点而被广泛研究。昆虫的半胱氨酸环配体门控离子通道也备受关注，因为它们是非常成功的杀虫剂的作用靶点。赤拟谷盗（Tribolium castaneum）是储存农产品的主要害虫，也是研究发育的重要模式生物。
作为赤拟谷盗基因组测序工作的一部分，我们已经对甲虫的半胱氨酸环配体门控离子通道超家族进行了表征，该超家族是继黑腹果蝇（Drosophila melanogaster）和意大利蜜蜂（Apis mellifera）之后被描述的第三个昆虫超家族，也是最大的超家族，由24个基因组成。与果蝇和蜜蜂一样，赤拟谷盗拥有由乙酰胆碱、γ-氨基丁酸（GABA）、谷氨酸和组胺门控的离子通道，以及果蝇pH敏感氯离子通道亚基（pHCl）、CG8916和CG12344的直系同源物。与果蝇和蜜蜂相似，赤拟谷盗的半胱氨酸环配体门控离子通道的多样性通过可变剪接得以扩展，尽管RDL和GluCl的甲虫直系同源物具有更多的外显子3变体。此外，在两个赤拟谷盗烟碱型乙酰胆碱受体亚基Tcasalpha6和Tcasbeta1中观察到了RNA A到I的编辑。Tcasalpha6中的编辑在进化上与黑腹果蝇、意大利蜜蜂和棉铃虫（Heliothis virescens）保守，而Tcasbeta1在一个迄今为止仅在甲虫中观察到的位点进行编辑。
我们的研究结果表明，在不同的昆虫物种中，半胱氨酸环配体门控离子通道超家族的基因数量仅发生了微小变化，保持了相对紧凑的状态。然而，可变剪接、RNA编辑以及不同亚基的存在扩展了半胱氨酸环配体门控离子通道的蛋白质组，并产生了物种特异性的受体亚型。这些关于赤拟谷盗的研究结果增强了我们对半胱氨酸环配体门控离子通道功能基因组学的理解，并为开发针对一种重要农业害虫的改良杀虫剂提供了有用的基础。
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