The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor
The Legionella pneumophila effector protein DrrA is a Rab1 guanine nucleotide-exchange factor
复制标题
DOI：
10.1038/ncb1463
复制
发表时间：
2006-09-01
影响因子：
21.3
通讯作者：
Roy, Craig R.
中科院分区：
文献类型：
--
作者：
Murata, Takahiro;Delprato, Anna;Roy, Craig R.
细胞内病原体嗜肺军团菌避免与溶酶体融合，并破坏内质网的膜转运，以产生支持细菌复制的细胞器（1，2）。内质网衍生的囊泡转运至含军团菌的液泡（LCV）需要细菌蛋白通过称为Dot/Icm的IV型分泌装置转运至宿主细胞（3-7）。最近的观察表明，宿主GTCRab 1通过一个需要Dot/Icm系统的过程被募集到LCV中（8，9）。在这里，使用视觉屏幕来识别L。在Rab 1募集中具有缺陷的嗜肺突变体。在该筛选中鉴定的因子之一是DrrA，一种新的转运到宿主细胞中的Dot/Icm底物蛋白。我们表明，DrrA是一种有效的和高度特异性Rab 1鸟嘌呤核苷酸交换因子（GEF）。DrrA可以破坏Rab 1介导的分泌运输到高尔基体的竞争与内源性交换因子招募和激活Rab 1的质膜衍生的细胞器。这些数据表明，细胞内病原体有能力直接调节特定成员的Rab家族的GTP酶的激活状态，从而进一步了解细菌病原体操纵宿主囊泡运输的机制。
The intracellular pathogen Legionella pneumophila avoids fusion with lysosomes and subverts membrane transport from the endoplasmic reticulum to create an organelle that supports bacterial replication(1,2). Transport of endoplasmic reticulum-derived vesicles to the Legionella-containing vacuole ( LCV) requires bacterial proteins that are translocated into host cells by a type IV secretion apparatus called Dot/Icm(3-7). Recent observations have revealed recruitment of the host GTPase Rab1 to the LCV by a process requiring the Dot/Icm system(8,9). Here, a visual screen was used to identify L. pneumophila mutants with defects in Rab1 recruitment. One of the factors identified in this screen was DrrA, a new Dot/Icm substrate protein translocated into host cells. We show that DrrA is a potent and highly specific Rab1 guanine nucleotide-exchange factor ( GEF). DrrA can disrupt Rab1-mediated secretory transport to the Golgi apparatus by competing with endogenous exchange factors to recruit and activate Rab1 on plasma membrane-derived organelles. These data establish that intracellular pathogens have the capacity to directly modulate the activation state of a specific member of the Rab family of GTPases and thus further our understanding of the mechanisms used by bacterial pathogens to manipulate host vesicular transport.