Dumoux Maud, Menny Anais, Delacour Delphine, Hayward Richard D
Institute of Structural and Molecular Biology, Birkbeck and University College London, Malet Street, London WC1E 7HX, UK.
Cell Adhesion and Mechanics Group, Institut Jacques Monod, CNRS UMR7592, Université Paris Diderot, 15 rue Helene Brion, Paris 75013, France.
J Cell Sci. 2015 Sep 15;128(18):3420-34. doi: 10.1242/jcs.169318. Epub 2015 Jul 28.
The obligate intracellular bacterial pathogen Chlamydia trachomatis deploys virulence effectors to subvert host cell functions enabling its replication within a specialized membrane-bound compartment termed an inclusion. The control of the host cytoskeleton is crucial for Chlamydia uptake, inclusion biogenesis and cell exit. Here, we demonstrate how a Chlamydia effector rearranges the microtubule (MT) network by initiating organization of the MTs at the inclusion surface. We identified an inclusion-localized effector that is sufficient to interfere with MT assembly, which we named inclusion protein acting on MTs (IPAM). We established that IPAM recruits and stimulates the centrosomal protein 170 kDa (CEP170) to hijack the MT organizing functions of the host cell. We show that CEP170 is essential for chlamydial control of host MT assembly, and is required for inclusion morphogenesis and bacterial infectivity. Together, we demonstrate how a pathogen effector reprograms the host MT network to support its intracellular development.
专性胞内细菌病原体沙眼衣原体利用毒力效应蛋白来破坏宿主细胞功能,使其能够在称为包涵体的特殊膜结合区室内进行复制。宿主细胞骨架的控制对于衣原体的摄取、包涵体生物发生和细胞逸出至关重要。在此,我们展示了一种衣原体效应蛋白如何通过在包涵体表面启动微管(MT)的组织来重新排列微管网络。我们鉴定出一种定位于包涵体的效应蛋白,它足以干扰微管组装,我们将其命名为作用于微管的包涵体蛋白(IPAM)。我们确定IPAM招募并刺激中心体蛋白170 kDa(CEP170)来劫持宿主细胞的微管组织功能。我们表明CEP170对于衣原体对宿主微管组装的控制至关重要,并且是包涵体形态发生和细菌感染性所必需的。我们共同展示了病原体效应蛋白如何重新编程宿主微管网络以支持其细胞内发育。