Drosophila immunity:: A large-scale in vivo RNAi screen identifies five serine proteases required for toll activation
Drosophila immunity:: A large-scale in vivo RNAi screen identifies five serine proteases required for toll activation
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DOI：
10.1016/j.cub.2006.03.020
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发表时间：
2006-04-18
期刊：
影响因子：
9.2
通讯作者：
Lemaitre, B
中科院分区：
文献类型：
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作者：
Kambris, Z;Brun, S;Lemaitre, B
与哺乳动物的Toll样受体不同，果蝇Toll受体不直接与微生物决定簇相互作用，而是在结合裂解形式的细胞因子样分子Spatzle(SPZ)时被激活。在免疫反应中，SPZ被认为是由血淋巴中分泌的丝氨酸蛋白酶(SPS)处理的，这些SPS被革兰氏阳性细菌或真菌的识别激活[1]。在目前的研究中，我们使用了体内RNAi策略来灭活75个不同的果蝇SP基因。然后，我们筛选了这些收集的SPS，以调节革兰氏阳性细菌激活Toll途径。在这里，我们报告了五个新的SP的鉴定，它们在将识别蛋白GNBP1和PGRP-SA连接到SPZ的细胞外途径中发挥功能。有趣的是，其中四个基因也是真菌激活Toll所必需的，而一个基因专门与响应革兰氏阳性细菌感染的信号有关。这些结果表明，SPZ上游存在一个共同的SP级联，通过更专门的SP整合各种分泌识别分子发出的信号。
Unlike mammalian Toll-like Receptors, the Drosophila Toll receptor does not interact directly with microbial determinants but is rather activated upon binding a cleaved form of the cytokine-like molecule Spatzle (Spz). During the immune response, Spz is thought to be processed by secreted serine proteases (SPs) present in the hemolymph that are activated by the recognition of gram-positive bacteria or fungi [1]. In the present study, we have used an in vivo RNAi strategy to inactivate 75 distinct Drosophila SP genes. We then screened this collection for SPs regulating the activation of the Toll pathway by gram-positive bacteria. Here, we report the identification of five novel SPs that function in an extracellular pathway linking the recognition proteins GNBP1 and PGRP-SA to Spz. Interestingly, four of these genes are also required for Toll activation by fungi, while one is specifically associated with signaling in response to gram-positive bacterial infections. These results demonstrate the existence of a common cascade of SPs upstream of Spz, integrating signals sent by various secreted recognition molecules via more specialized SPs.