Legionella subvert the functions of Rab1 and Sec22b to create a replicative organelle

被引:234
作者
Kagan, JC [1 ]
Stein, MP [1 ]
Pypaert, M [1 ]
Roy, CR [1 ]
机构
[1] Yale Univ, Sch Med, Boyer Ctr Mol Med, Sect Microbial Pathogenesis, New Haven, CT 06536 USA
关键词
brefeldin A; ARF1; Sar1; phagosome; endoplasmic reticulum;
D O I
10.1084/jem.20031706
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Legionella pneumophila is a bacterial pathogen that infects eukaryotic host cells and replicates inside a specialized organelle that is morphologically similar to the endoplasmic reticulum (ER). To better understand the molecular mechanisms governing transport of the Legionella-containing vacuole (LCV), we have identified host proteins that participate in the conversion of the LCV into a replicative organelle. Our data show that Rab1 is recruited to the LCV within minutes of uptake. Rab1 recruitment to the LCV precedes remodeling of this compartment by ER-derived vesicles. Genetic inhibition studies demonstrate that Rab1 is important for the recruitment of ER-derived vesicles to the LCV and that inhibiting Rab1 function abrogates intracellular growth of Legionella. Morphological studies Indicate that the Sec22b protein is located on EK-derived vesicles recruited to the LCV and that Sec22b is delivered to the LCV membrane. Sec22b function was found to be important for biogenesis of the specialized organelle that supports Legionella replication. These studies demonstrate that Legionella has the ability to subvert Rab1 and Sec22b function to facilitate the transport and fusion of ER-derived vesicles with the LCV, resulting in the formation of a specialized organelle that can support bacterial replication.
引用
收藏
页码:1201 / 1211
页数:11
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