Parker J S, Mizuguchi K, Gay N J
Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
Proteins. 2001 Oct 1;45(1):71-80. doi: 10.1002/prot.1125.
The Drosophila gene Spätzle encodes the activating ligand for the Toll receptor. This signaling pathway is required for dorso-ventral patterning in the early embryo and an antifungal immune response in larvae and adults. The genome sequence of Drosophila shows that there are a total of eight Toll-like receptors and these may function in other aspects of embryonic development and innate immunity. Here we describe five Drosophila homologues of Spätzle (Spz2-6) found using an iterative searching method. All five appear to encode proteins containing neurotrophin-like cystine-knot domains. In addition, most retain a characteristic intron-exon structure shared with the prototype Spätzle gene. This provides evidence that the family arose by ancient gene duplication events and indicates that the gene products may represent activating ligands for corresponding Toll receptors. Expression studies show that only Spz4 is expressed strongly in larvae and adults and thus may be involved in an ancillary antifungal response mediated by Toll-5. By contrast, Spz6 shows a complex spatial and temporally regulated expression pattern in the late embryo. Thus the new Toll/Spätzle families of signaling molecules may have important roles in other aspects of development and immunity.
果蝇基因斯帕特氏蛋白（Spätzle）编码Toll受体的激活配体。该信号通路在早期胚胎的背腹模式形成以及幼虫和成虫的抗真菌免疫反应中是必需的。果蝇的基因组序列显示共有八个Toll样受体，它们可能在胚胎发育和先天免疫的其他方面发挥作用。在这里，我们描述了使用迭代搜索方法发现的五个斯帕特氏蛋白（Spätzle）的果蝇同源物（Spz2 - 6）。所有这五个似乎都编码含有神经营养因子样胱氨酸结结构域的蛋白质。此外，大多数保留了与原型斯帕特氏蛋白基因共有的特征性内含子 - 外显子结构。这提供了证据表明该家族是由古代基因复制事件产生的，并表明基因产物可能代表相应Toll受体的激活配体。表达研究表明，只有Spz4在幼虫和成虫中强烈表达，因此可能参与由Toll - 5介导的辅助抗真菌反应。相比之下，Spz6在晚期胚胎中显示出复杂的时空调节表达模式。因此，新的Toll/斯帕特氏蛋白信号分子家族可能在发育和免疫的其他方面具有重要作用。
