The Chlamydia trachomatis Tarp effector targets the Hippo pathway.
The Chlamydia trachomatis Tarp effector targets the Hippo pathway.
复制标题
DOI：
10.1016/j.bbrc.2021.05.057
复制
发表时间：
2021-07-12
影响因子：
3.1
通讯作者：
Jewett TJ
中科院分区：
文献类型：
--
作者：
Shehat MG;Aranjuez GF;Kim J;Jewett TJ
沙眼衣原体将细菌效应蛋白注入人类上皮细胞，以促进新感染的建立。衣原体III型分泌效应转位的肌动蛋白募集磷蛋白(TARP)已被证明能使肌动蛋白细丝成核并成束。它还被认为通过N-末端的磷酸化结构域启动新的信号通路。对TARP控制的宿主途径以帮助建立成功感染的全面了解仍然不完整。为了进一步了解Tarp调控的细胞信号转导，我们培育了表达Tarp N-末端结构域的转基因果蝇。由于果蝇和哺乳动物之间的许多信号通路是保守的，我们推测在果蝇中Tarp N-结构域的表达可能会扰乱关键的信号通路，导致发育缺陷。TARP N结构域在果蝇中的表达导致了机械感觉刷毛的复制表型，类似于先前发现的由河马途径缺陷引起的果蝇表型。在沙眼衣原体组织培养感染模型中证实了TARP依赖的河马途径的中断。TARP在感染的上皮细胞中改变Hippo途径信号的能力是衣原体以前未知的途径，可能有助于衣原体细胞内生态位的建立。
Chlamydia trachomatis injects bacterial effector proteins into human epithelial cells to facilitate the establishment of new infections. The chlamydial type III secreted effector translocated actin recruiting phosphoprotein (Tarp) has been shown to nucleate and bundle actin filaments. It is also believed to initiate new signaling pathways via an N-terminal phosphorylation domain. A comprehensive understanding of the host pathways that are controlled by Tarp to aid in the establishment of a successful infection remains incomplete. To gain further insight into the cell signaling regulated by Tarp, we generated transgenic fruit flies engineered to express the N-terminal domain of Tarp. As many signaling pathways are conserved between flies and mammals, we hypothesized that expression of the Tarp N-domain in the fruit fly might disrupt key pathways, resulting in developmental defects. Tarp N-domain expression in the fruit fly resulted in a mechanosensory bristle duplication phenotype similar to a previously characterized fly phenotype found to be a consequence of defects in the Hippo pathway. Tarp-dependent disruption of the Hippo pathway was confirmed in a C. trachomatis tissue culture infection model. The capability of Tarp to alter Hippo pathway signaling in infected epithelial cells is a previously unrecognized pathway commandeered by chlamydia and likely contributes to the establishment of chlamydia’s intracellular niche.
登录
查看更多内容
DOI：
10.1073/pnas.0603044103
发表时间：
2006-10-17
影响因子：
11.1
作者：
Jewett, Travis J.;Fischer, Elizabeth R.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted
影响因子：
2.1
作者：
Mehlitz, Adrian;Banhart, Sebastian;Meyer, Thomas F.
通讯作者：
Meyer, Thomas F.
影响因子：
--
作者：
Scidmore, Marci A
通讯作者：
Scidmore, Marci A
影响因子：
9
作者：
Wang, Lan-Hsin;Baker, Nicholas E.
通讯作者：
Baker, Nicholas E.
DOI：
10.1016/j.bbrc.2008.04.089
发表时间：
2008-06-27
影响因子：
3.1
作者：
Jewett, Travis J.;Dooley, Cheryl A.;Hackstadt, Ted
通讯作者：
Hackstadt, Ted