p62 and NDP52 Proteins Target Intracytosolic Shigella and Listeria to Different Autophagy Pathways
p62 and NDP52 Proteins Target Intracytosolic Shigella and Listeria to Different Autophagy Pathways
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DOI：
10.1074/jbc.m111.223610
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发表时间：
2011-07-29
影响因子：
4.8
通讯作者：
Cossart, Pascale
中科院分区：
文献类型：
--
作者：
Mostowy, Serge;Sancho-Shimizu, Vanessa;Cossart, Pascale
自噬是天然免疫防御的重要机制。我们最近发现，自噬成分与septins，一个新的和越来越多的特点的细胞骨架成分，胞内志贺菌，已开始reactin招募。另一方面，胞内李斯特菌通过表达肌动蛋白聚合所需的细菌效应子ActA来避免自噬识别。在这里，我们利用志贺氏菌和李斯特菌作为胞内工具来表征选择性自噬的不同途径。我们发现，泛素结合衔接蛋白p62和NDP 52的目标志贺氏菌的自噬途径依赖于隔蛋白和肌动蛋白。相比之下，p62或NDP 52将李斯特菌ActA突变体靶向不依赖于隔蛋白或肌动蛋白的自噬途径。TNF-α是细菌感染后产生的宿主细胞因子，刺激p62介导的自噬活性并限制志贺氏菌和李斯特菌ActA突变体的存活。这些数据提供了一个新的分子框架，以了解新出现的自噬的复杂性及其实现胞内细菌特异性清除的能力。
Autophagy is an important mechanism of innate immune defense. We have recently shown that autophagy components are recruited with septins, a new and increasingly characterized cytoskeleton component, to intracytosolic Shigella that have started to polymerize actin. On the other hand, intracytosolic Listeria avoids autophagy recognition by expressing ActA, a bacterial effector required for actin polymerization. Here, we exploit Shigella and Listeria as intracytosolic tools to characterize different pathways of selective autophagy. We show that the ubiquitin-binding adaptor proteins p62 and NDP52 target Shigella to an autophagy pathway dependent upon septin and actin. In contrast, p62 or NDP52 targets the Listeria ActA mutant to an autophagy pathway independent of septin or actin. TNF-alpha, a host cytokine produced upon bacterial infection, stimulates p62-mediated autophagic activity and restricts the survival of Shigella and the Listeria ActA mutant. These data provide a new molecular framework to understand the emerging complexity of autophagy and its ability to achieve specific clearance of intracytosolic bacteria.