Legionella remodels the plasma membrane-derived vacuole by utilizing exocyst components as tethers.
Legionella remodels the plasma membrane-derived vacuole by utilizing exocyst components as tethers.
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DOI：
10.1083/jcb.201801208
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发表时间：
2018-11-05
期刊：
影响因子：
--
通讯作者：
Roy CR
中科院分区：
文献类型：
--
作者：
Arasaki K;Kimura H;Tagaya M;Roy CR
嗜肺军团菌在质膜衍生的液泡中进入细胞，然后将囊泡从内质网隔离，以支持寄生虫的生长和免疫逃避。Arasaki et al.现在揭示军团菌效应器DrrA招募排囊的组件来促进宿主囊泡与LCV的捆绑。在感染的最初阶段，嗜肺军团菌会分泌效应器，促进内质网(ER)来源的小泡与含有军团菌的空泡(LCV)融合。这种融合导致质膜(PM)来源的LCV重塑为支持细菌复制的专门的内质网样隔室。尽管效应器DrrA已被证明激活小GTP酶Rab1，但仍不清楚DrrA如何促进宿主囊泡与LCV的连接。在这里，我们证明了Sec5，Sec15，或者Sec6，它们是胞外囊的亚单位，在胞外囊泡与PM的连接中起作用，是DrrA介导的内质网衍生的囊泡重新聚集到PM来源的LCV所必需的。这些外囊成分被发现与含有DrrA的复合体特异性地相互作用，而Sec5或Sec15的缺失显著抑制了内质网衍生的囊泡向LCV的募集，并抑制了军团菌的细胞内复制。重要的是，Sec15被招募到LCV，而Rab1的激活是这次招募所必需的。
Legionella pneumophila enters cells in a vacuole derived from the plasma membrane, which then sequesters vesicles from the ER in order to support parasite growth and immune evasion. Arasaki et al. now reveal that the Legionella effector DrrA recruits components of the exocyst to promote tethering of host vesicles with the LCV. During the initial stage of infection, Legionella pneumophila secretes effectors that promote the fusion of endoplasmic reticulum (ER)–derived vesicles with the Legionella-containing vacuole (LCV). This fusion leads to a remodeling of the plasma membrane (PM)–derived LCV into a specialized ER-like compartment that supports bacterial replication. Although the effector DrrA has been shown to activate the small GTPase Rab1, it remains unclear how DrrA promotes the tethering of host vesicles with the LCV. Here, we show that Sec5, Sec15, and perhaps Sec6, which are subunits of the exocyst that functions in the tethering of exocytic vesicles with the PM, are required for DrrA-mediated, ER-derived vesicle recruitment to the PM-derived LCV. These exocyst components were found to interact specifically with a complex containing DrrA, and the loss of Sec5 or Sec15 significantly suppressed the recruitment of ER-derived vesicles to the LCV and inhibited intracellular replication of Legionella. Importantly, Sec15 is recruited to the LCV, and Rab1 activation is necessary for this recruitment.
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DOI：
10.1084/jem.158.6.2108
发表时间：
1983-12-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Horwitz MA
通讯作者：
Horwitz MA
影响因子：
30.3
作者：
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影响因子：
56.9
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影响因子：
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影响因子：
16.8
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