Vassilatis D K, Elliston K O, Paress P S, Hamelin M, Arena J P, Schaeffer J M, Van der Ploeg L H, Cully D F
Department of Genetics and Molecular Biology, RY80Y-305, Merck Research Laboratories, P.O. Box 2000, Rahway, NJ 07065-0900, USA.
J Mol Evol. 1997 May;44(5):501-8. doi: 10.1007/pl00006174.
Two cDNAs, GluClalpha and GluClbeta, encoding glutamate-gated chloride channel subunits that represent targets of the avermectin class of antiparasitic compounds, have recently been cloned from Caenorhabditis elegans (Cully et al., Nature, 371, 707-711, 1994). Expression studies in Xenopus oocytes showed that GluClalpha and GluClbeta have pharmacological profiles distinct from the glutamate-gated cation channels as well as the gamma-aminobutyric acid (GABA)- and glycine-gated chloride channels. Establishing the evolutionary relationship of related proteins can clarify properties and lead to predictions about their structure and function. We have cloned and determined the nucleotide sequence of the GluClalpha and GluClbeta genes. In an attempt to understand the evolutionary relationship of these channels with the members of the ligand-gated ion channel superfamily, we have performed gene structure comparisons and phylogenetic analyses of their nucleotide and predicted amino acid sequences. Gene structure comparisons reveal the presence of several intron positions that are not found in the ligand-gated ion channel superfamily, outlining their distinct evolutionary position. Phylogenetic analyses indicate that GluClalpha and GluClbeta form a monophyletic subbranch in the ligand-gated ion channel superfamily and are related to vertebrate glycine channels/receptors. Glutamate-gated chloride channels, with electrophysiological properties similar to GluClalpha and GluClbeta, have been described in insects and crustaceans, suggesting that the glutamate-gated chloride channel family may be conserved in other invertebrate species. The gene structure and phylogenetic analyses in combination with the distinct pharmacological properties demonstrate that GluClalpha and GluClbeta belong to a discrete ligand-gated ion channel family that may represent genes orthologous to the vertebrate glycine channels.
两个编码谷氨酸门控氯离子通道亚基的cDNA，即GluClα和GluClβ，它们是抗寄生虫化合物阿维菌素类的作用靶点，最近已从秀丽隐杆线虫中克隆出来（Cully等人，《自然》，371卷，707 - 711页，1994年）。在非洲爪蟾卵母细胞中的表达研究表明，GluClα和GluClβ具有与谷氨酸门控阳离子通道以及γ - 氨基丁酸（GABA）和甘氨酸门控氯离子通道不同的药理学特征。确定相关蛋白质的进化关系可以阐明其特性，并有助于预测它们的结构和功能。我们已经克隆并测定了GluClα和GluClβ基因的核苷酸序列。为了试图理解这些通道与配体门控离子通道超家族成员之间的进化关系，我们对它们的核苷酸和预测的氨基酸序列进行了基因结构比较和系统发育分析。基因结构比较揭示了在配体门控离子通道超家族中未发现的几个内含子位置，勾勒出它们独特的进化位置。系统发育分析表明，GluClα和GluClβ在配体门控离子通道超家族中形成一个单系亚分支，并且与脊椎动物的甘氨酸通道/受体相关。在昆虫和甲壳类动物中已经描述了具有与GluClα和GluClβ相似电生理特性的谷氨酸门控氯离子通道，这表明谷氨酸门控氯离子通道家族可能在其他无脊椎动物物种中保守。基因结构和系统发育分析与独特的药理学特性相结合表明，GluClα和GluClβ属于一个离散的配体门控离子通道家族，可能代表与脊椎动物甘氨酸通道直系同源的基因。
