A post-invasion role for Chlamydia type III effector TarP in modulating the dynamics and organization of host cell focal adhesions.
A post-invasion role for Chlamydia type III effector TarP in modulating the dynamics and organization of host cell focal adhesions.
复制标题
衣原体III型效应器TarP在调节宿主细胞粘着斑的动力学和组织中的侵袭后作用
DOI：
10.1074/jbc.ra120.015219
复制
发表时间：
2020-10-23
期刊：
影响因子：
--
通讯作者：
Carabeo RA
中科院分区：
文献类型：
--
作者：
Pedrosa AT;Murphy KN;Nogueira AT;Brinkworth AJ;Thwaites TR;Aaron J;Chew TL;Carabeo RA
人类病原体沙眼衣原体的目标是生殖器粘膜的上皮细胞。我们观察到，各种类型的细胞，包括成纤维细胞和上皮细胞的感染导致异常稳定和成熟的局灶性粘连的形成，抵抗由肌球蛋白II抑制剂，blebbistatin诱导的解体。超分辨率显微镜显示，在感染的细胞中，桩蛋白和粘着斑激酶从粘着斑信号层垂直位移，而纽蛋白则保持在力传递层内的正常位置。候选III型效应器TarP，其在感染期间定位于局灶性粘连，并且当异位表达时，足以模拟重组和blebbistatin-resistant表型。这些影响的TarP，包括其本地化的局灶性粘连，需要一个入侵后的相互作用与宿主蛋白粘着斑蛋白通过一个特定的域在C末端的TarP。这种相互作用被重新利用，从肌动蛋白募集和重塑复合物到介导局灶性粘连的纳米结构和动态变化的复合物。衣原体稳定的局灶性粘连的后果是限制细胞运动和增强附着的细胞外基质。因此，通过一种新的机制，衣原体将TarP插入局灶性粘连中，以改变其组织和稳定性。
The human pathogen Chlamydia trachomatis targets epithelial cells lining the genital mucosa. We observed that infection of various cell types, including fibroblasts and epithelial cells resulted in the formation of unusually stable and mature focal adhesions that resisted disassembly induced by the myosin II inhibitor, blebbistatin. Superresolution microscopy revealed in infected cells the vertical displacement of paxillin and focal adhesion kinase from the signaling layer of focal adhesions, whereas vinculin remained in its normal position within the force transduction layer. The candidate type III effector TarP, which localized to focal adhesions during infection and when expressed ectopically, was sufficient to mimic both the reorganization and blebbistatin-resistant phenotypes. These effects of TarP, including its localization to focal adhesions, required a post-invasion interaction with the host protein vinculin through a specific domain at the C terminus of TarP. This interaction is repurposed from an actin-recruiting and -remodeling complex to one that mediates nanoarchitectural and dynamic changes of focal adhesions. The consequence of Chlamydia-stabilized focal adhesions was restricted cell motility and enhanced attachment to the extracellular matrix. Thus, via a novel mechanism, Chlamydia inserts TarP within focal adhesions to alter their organization and stability.
DOI：
10.1186/1476-9255-8-11
发表时间：
2011-05-03
期刊：
Journal of inflammation (London, England)
影响因子：
--
作者：
Vossenkämper A;Macdonald TT;Marchès O
通讯作者：
Marchès O