Chlamydia trachomatis plasmid-encoded protein pORF5 activates unfolded protein response to induce autophagy via MAPK/ERK signaling pathway
Chlamydia trachomatis plasmid-encoded protein pORF5 activates unfolded protein response to induce autophagy via MAPK/ERK signaling pathway
复制标题
沙眼衣原体质粒编码蛋白 pORF5 通过 MAPK/ERK 信号通路激活未折叠蛋白反应诱导自噬
DOI：
10.1016/j.bbrc.2020.04.117
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发表时间：
2020-06-30
影响因子：
3.1
通讯作者：
Li, Zhongyu
中科院分区：
文献类型：
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作者：
Wen, Yating;Luo, Fangzhen;Li, Zhongyu
沙眼衣原体（C.沙眼衣原体）是一种专性细胞内生物体，其依赖于来自宿主细胞的营养物进行复制和增殖。因此，这种病原体和宿主之间的相互作用在感染的细胞中诱导持续的内质网（ER）应激。解折叠蛋白反应（UPR）已被证明是由衣原体分泌的效应物激活，允许宿主细胞从应激状态中恢复。在本研究中，我们试图探讨C. UPR和自噬诱导之间的关系。结果表明，pORF 5激活了UPR的三个分支（PERK，IRE 1和ATF 6）。UPR抑制剂GSK 2606414和4 μ 8 C可抑制pORF 5诱导的自噬，但对pORF 5诱导的UPR无明显影响。MAPK/ERK抑制剂PD 98059可部分抑制pORF 5诱导的自噬，但对UPR影响不大，表明pORF 5通过MAPK/ERK信号通路激活UPR诱导自噬。这些观察结果为宿主在C.沙眼感染(C)2020爱思唯尔公司All rights reserved.
Chlamydia trachomatis (C. trachomatis) is an obligate intracellular organism that depends on nutrients from the host cell for their replication and proliferation. Therefore, the interaction between this pathogen and host induces sustained endoplasmic reticulum (ER) stress in the infected cells. Unfolded protein response (UPR) has been demonstrated to be activated by chlamydial secreted effectors, allowing host cells to recover from the stressful state. In this study, we attempted to explore the role of the only secreted plasmid-encoded protein pORF5 of C. trachomatis between UPR and autophagy induction. The results showed that three branches of UPR (PERK, IRE1, and ATF6) were activated by pORF5. pORF5-induced autophagy was repressed by UPR inhibitors GSK2606414 and 4 mu 8C, while the autophagy inhibition was failed to influence pORF5-induced UPR significantly. MAPK/ERK inhibitor PD98059 partially suppressed the pORF5-induced autophagy, but had little effect on UPR, indicating that pORF5 actives UPR to induce autophagy via the MAPK/ERK signaling pathway. These observations provide clues on how the host maintains the cellular homeostasis during C. trachomatis infection. (C) 2020 Elsevier Inc. All rights reserved.