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沙眼衣原体 CT229 颠覆 Rab GTPase 依赖的 CCV 运输途径以促进衣原体感染。

Chlamydia trachomatis CT229 Subverts Rab GTPase-Dependent CCV Trafficking Pathways to Promote Chlamydial Infection.

机构信息

Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA.

Department of Microbiology and Immunology, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA; Department of Biology, University of Dayton, Dayton, OH 45469, USA.

出版信息

Cell Rep. 2019 Mar 19;26(12):3380-3390.e5. doi: 10.1016/j.celrep.2019.02.079.

Abstract

Chlamydial infection requires the formation of a membrane-bound vacuole, termed the inclusion, that undergoes extensive interactions with select host organelles. The importance of the Inc protein CT229 in the formation and maintenance of the chlamydial inclusion was recently highlighted by studies demonstrating that its absence during infection results in reduced bacterial replication, premature inclusion lysis, and host cell death. Previous reports have indicated that CT229 binds Rab GTPases; however, the physiological implications of this interaction are unknown. Here, we show that CT229 regulates host multivesicular trafficking by recruiting multiple Rab GTPases and their cognate effectors to the inclusion. We demonstrate that CT229 specifically modulates clathrin-coated vesicle trafficking and regulates the trafficking of transferrin and the mannose-6-phosphate receptor, both of which are crucial for proper chlamydial development. This study highlights CT229 as a master regulator of multiple host vesicular trafficking pathways essential for chlamydial infection.

摘要

衣原体感染需要形成一个膜结合的空泡,称为包含体,它与特定的宿主细胞器进行广泛的相互作用。最近的研究强调了 Inc 蛋白 CT229 在包含体的形成和维持中的重要性,这些研究表明,在感染过程中缺乏 CT229 会导致细菌复制减少、包含体过早裂解和宿主细胞死亡。先前的报告表明 CT229 结合 Rab GTPases;然而,这种相互作用的生理意义尚不清楚。在这里,我们表明 CT229 通过招募多种 Rab GTPases 及其同源效应物到包含体上来调节宿主多泡体运输。我们证明 CT229 特异性调节网格蛋白包被小泡的运输,并调节转铁蛋白和甘露糖-6-磷酸受体的运输,这两者对于衣原体的正常发育都是至关重要的。这项研究强调了 CT229 作为多个宿主囊泡运输途径的主要调节剂的作用,这些途径对于衣原体感染是必不可少的。

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