Large-scale identification of Legionella pneumophila Dot/Icm substrates that modulate host cell vesicle trafficking pathways.
Large-scale identification of Legionella pneumophila Dot/Icm substrates that modulate host cell vesicle trafficking pathways.
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DOI：
10.1111/j.1462-5822.2008.01249.x
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发表时间：
2009-02
影响因子：
3.4
通讯作者：
Isberg RR
中科院分区：
文献类型：
--
作者：
Heidtman M;Chen EJ;Moy MY;Isberg RR
细菌病原体嗜肺军团菌在宿主细胞内的一个特殊空泡中复制。复制空泡的建立依赖于Dot/ICM易位系统，该系统将大量蛋白质底物输送到宿主细胞中。大多数底物的功能尚不清楚。在这里，我们使用酵母作为模型系统，分析了一组定义的127种已确认或候选的Dot/ICM底物对宿主细胞过程的影响。79个候选蛋白的表达导致了显著的酵母生长缺陷，表明这些蛋白影响了重要的宿主细胞途径。值得注意的是，一组21名候选人干扰了分泌蛋白向酵母液泡的运输。对引起酵母菌分泌缺陷的3个候选菌株(SetA、Ceg19和Ceg9)进行了进一步的研究。这些蛋白在不同的阶段影响囊泡运输，并具有允许Dot/ICM系统转位到宿主细胞的信号。异位产生的SetA、Ceg19和Ceg9定位于哺乳动物细胞的分泌细胞器，与这些蛋白在调节宿主细胞囊泡运输中的作用一致。有趣的是，SetA产生酵母表型的能力依赖于一个功能糖基转移酶结构域。我们推测，在嗜肺乳杆菌感染过程中，SetA可能使宿主细胞囊泡运输机制的一个组成部分糖基化。
The bacterial pathogen Legionella pneumophila replicates in a specialized vacuole within host cells. Establishment of the replication vacuole depends on the Dot/Icm translocation system that delivers a large number of protein substrates into the host cell. The functions of most substrates are unknown. Here, we analyzed a defined set of 127 confirmed or candidate Dot/Icm substrates for their effect on host cell processes using yeast as a model system. Expression of 79 candidates caused significant yeast growth defects, indicating these proteins impact essential host cell pathways. Notably, a group of 21 candidates interfered with the trafficking of secretory proteins to the yeast vacuole. Three candidates that caused yeast secretory defects (SetA, Ceg19 and Ceg9) were investigated further. These proteins impinged upon vesicle trafficking at distinct stages and had signals that allowed translocation into host cells by the Dot/Icm system. Ectopically produced SetA, Ceg19 and Ceg9 localized to secretory organelles in mammalian cells, consistent with a role for these proteins in modulating host cell vesicle trafficking. Interestingly, the ability of SetA to cause yeast phenotypes was dependent upon a functional glycosyltransferase domain. We hypothesize that SetA may glycosylate a component of the host cell vesicle trafficking machinery during L. pneumophila infection.
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影响因子：
4.8
作者：
Belden, WJ;Barlowe, C
通讯作者：
Barlowe, C
影响因子：
3.6
作者：
Bardill, JP;Miller, JL;Vogel, JP
通讯作者：
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作者：
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Ploegh HL
影响因子：
3.6
作者：
Duménil, G;Isberg, RR
通讯作者：
Isberg, RR