A spatzle-processing enzyme required for toll signaling activation in Drosophila innate immunity

A spatzle-processing enzyme required for toll signaling activation in Drosophila innate immunity
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DOI:
10.1016/j.devcel.2005.11.013
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发表时间:
2006-01-01
期刊:
影响因子:
11.8
通讯作者:
Lee, WJ
Lee, WJ
中科院分区:
生物学1区
文献类型:
--
作者:
Jang, IH;Chosa, N;Lee, WJ

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Toll受体最初被认为是果蝇胚胎发育中不可或缺的分子,随后被认为是昆虫对人类先天免疫的重要组成部分。尽管在果蝇中,复活节蛋白酶在发育过程中加工前spatzle蛋白以产生Toll配体,但在免疫应答过程中负责前spatzle加工的蛋白酶的鉴定十年来仍然难以捉摸。在这里,我们报告了一种蛋白酶,称为sp5tzle加工酶(SPE),它是toll依赖性抗菌反应所必需的。SPE表达减少的果蝇没有明显的spatle前加工,对微生物感染高度敏感。此外,激活的SPE可以挽救缺乏Easter的胚胎的腹侧发育,表明SPE与Easter在功能上具有同源性。这些结果表明,通过招募具有不同激活模式的相似配体加工蛋白酶,单个配体/受体介导的信号事件可用于不同的生物过程,如免疫和发育。
The Toll receptor was originally identified as an indispensable molecule for Drosophila embryonic development and subsequently as an essential component of innate immunity from insects to humans. Although in Drosophila the Easter protease processes the pro-Spatzle protein to generate the Toll ligand during development, the identification of the protease responsible for pro-Spatzle processing during the immune response has remained elusive for a decade. Here, we report a protease, called Sp5tzle-processing enzyme (SPE), required for Toll-dependent antimicrobial response. Flies with reduced SPE expression show no noticeable pro-Spatzle processing and become highly susceptible to microbial infection. Furthermore, activated SPE can rescue ventral and lateral development in embryos lacking Easter, showing the functional homology between SPE and Easter. These results imply that a single ligand/receptor-mediated signaling event can be utilized for different biological processes, such as immunity and development, by recruiting similar ligand-processing proteases with distinct activation modes.