Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning.
Chlamydia Hijacks ARF GTPases To Coordinate Microtubule Posttranslational Modifications and Golgi Complex Positioning.
复制标题
DOI：
10.1128/mbio.02280-16
复制
发表时间：
2017-05-02
期刊：
影响因子：
6.4
通讯作者：
Paumet F
中科院分区：
文献类型：
--
作者：
Wesolowski J;Weber MM;Nawrotek A;Dooley CA;Calderon M;St Croix CM;Hackstadt T;Cherfils J;Paumet F
细胞内细菌沙眼衣原体在称为包涵体的寄生隔室中生长。翻译后修饰的微管包裹着包涵体，控制着包涵体周围高尔基复合物片段的定位。衣原体利用宿主细胞骨架和高尔基复合体维持其感染室的分子机制尚不清楚。在这里，我们使用转基因衣原体菌株，发现翻译后修饰的微管和包裹体周围的高尔基复合体定位都受到衣原体包裹体蛋白CT813/CTL0184/InaC和宿主ARF GTPases的控制。CT813将ARF1和ARF4招募到包涵膜，在那里它们诱导翻译后修饰的微管。同样，这两种ARF异构体都需要在包含物周围重新定位高尔基复合体片段。我们证明CT813直接在包合膜上募集ARF gtpase，并在其激活中起关键作用。总之，这些结果表明衣原体利用CT813劫持ARF gtpase，将翻译后修饰的微管和高尔基复合体偶联在包涵体上。沙眼衣原体是世界上发病率和经济负担的重要原因。然而，衣原体如何形成其细胞内腔室，即所谓的包涵体，人们知之甚少。利用基因工程衣原体突变体，我们发现效应蛋白CT813招募并激活宿主adp -核糖基化因子1 （ARF1）和ARF4来调节微管。在这种情况下，CT813作为分子平台诱导包涵体周围微管的翻译后修饰。这些笼然后用于在感染期间重新定位高尔基体复合体并促进包涵体的发育。该研究首次证明ARF1和ARF4在控制包涵体周围翻译后修饰的微管中发挥关键作用，并且沙眼衣原体劫持了ARF的这种新功能来重新定位高尔基复合体。
The intracellular bacterium Chlamydia trachomatis develops in a parasitic compartment called the inclusion. Posttranslationally modified microtubules encase the inclusion, controlling the positioning of Golgi complex fragments around the inclusion. The molecular mechanisms by which Chlamydia coopts the host cytoskeleton and the Golgi complex to sustain its infectious compartment are unknown. Here, using a genetically modified Chlamydia strain, we discovered that both posttranslationally modified microtubules and Golgi complex positioning around the inclusion are controlled by the chlamydial inclusion protein CT813/CTL0184/InaC and host ARF GTPases. CT813 recruits ARF1 and ARF4 to the inclusion membrane, where they induce posttranslationally modified microtubules. Similarly, both ARF isoforms are required for the repositioning of Golgi complex fragments around the inclusion. We demonstrate that CT813 directly recruits ARF GTPases on the inclusion membrane and plays a pivotal role in their activation. Together, these results reveal that Chlamydia uses CT813 to hijack ARF GTPases to couple posttranslationally modified microtubules and Golgi complex repositioning at the inclusion. Chlamydia trachomatis is an important cause of morbidity and a significant economic burden in the world. However, how Chlamydia develops its intracellular compartment, the so-called inclusion, is poorly understood. Using genetically engineered Chlamydia mutants, we discovered that the effector protein CT813 recruits and activates host ADP-ribosylation factor 1 (ARF1) and ARF4 to regulate microtubules. In this context, CT813 acts as a molecular platform that induces the posttranslational modification of microtubules around the inclusion. These cages are then used to reposition the Golgi complex during infection and promote the development of the inclusion. This study provides the first evidence that ARF1 and ARF4 play critical roles in controlling posttranslationally modified microtubules around the inclusion and that Chlamydia trachomatis hijacks this novel function of ARF to reposition the Golgi complex.