Beyond Rab GTPases Legionella activates the small GTPase Ran to promote microtubule polymerization, pathogen vacuole motility, and infection.
Beyond Rab GTPases Legionella activates the small GTPase Ran to promote microtubule polymerization, pathogen vacuole motility, and infection.
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DOI：
10.4161/21541248.2014.972859
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发表时间：
2014-01-01
期刊：
影响因子：
--
通讯作者：
Harrison, Christopher F
中科院分区：
文献类型：
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作者：
Hilbi, Hubert;Rothmeier, Eva;Harrison, Christopher F
军团菌属是一种抗阿米巴原虫的环境细菌，它们在一个不同的隔室（含军团菌的液泡（LCV））中的自由生活的原生动物中复制。在嗜肺军团菌传播到肺部后，病原体采用进化上保守的机制在肺泡巨噬细胞内的LCV中生长，从而引发称为军团病的严重肺炎。LCV的形成是一个复杂而强大的过程，它需要细菌的Icm/Dot IV型分泌系统，并涉及数量惊人的300种不同的易位效应蛋白。LCV与宿主细胞的内体和分泌囊泡运输途径相互作用。因此，在蛋白质组学方法中，多达12种涉及内体和分泌囊泡运输的小Rab GTP酶被鉴定并验证为LCV组分。此外，已发现小的GTdR Ran及其效应蛋白RanBP 1装饰病原体液泡。RAN调节核质转运、纺锤体组装和胞质分裂，以及非中心体微管的组织。在洛在嗜肺菌感染的阿米巴原虫或巨噬细胞中，Ran和RanBP 1定位于LCV，并且小GT3由Icm/Dot底物LegG 1激活。Ran通过LegG 1激活导致微管稳定并促进细胞内病原体空泡运动和细菌生长，以及军团菌感染细胞的趋化性和迁移。
Legionella spp. are amoebae-resistant environmental bacteria that replicate in free-living protozoa in a distinct compartment, the Legionella-containing vacuole (LCV). Upon transmission of Legionella pneumophila to the lung, the pathogens employ an evolutionarily conserved mechanism to grow in LCVs within alveolar macrophages, thus triggering a severe pneumonia termed Legionnaires' disease. LCV formation is a complex and robust process, which requires the bacterial Icm/Dot type IV secretion system and involves the amazing number of 300 different translocated effector proteins. LCVs interact with the host cell's endosomal and secretory vesicle trafficking pathway. Accordingly, in a proteomics approach as many as 12 small Rab GTPases implicated in endosomal and secretory vesicle trafficking were identified and validated as LCV components. Moreover, the small GTPase Ran and its effector protein RanBP1 have been found to decorate the pathogen vacuole. Ran regulates nucleo-cytoplasmic transport, spindle assembly, and cytokinesis, as well as the organization of non-centrosomal microtubules. In L. pneumophila-infected amoebae or macrophages, Ran and RanBP1 localize to LCVs, and the small GTPase is activated by the Icm/Dot substrate LegG1. Ran activation by LegG1 leads to microtubule stabilization and promotes intracellular pathogen vacuole motility and bacterial growth, as well as chemotaxis and migration of Legionella-infected cells.