Anaplasma phagocytophilum AptA enhances the UPS, autophagy, and anti-apoptosis of host cells by PSMG3
Anaplasma phagocytophilum AptA enhances the UPS, autophagy, and anti-apoptosis of host cells by PSMG3
复制标题
嗜吞噬细胞无形体 AptA 通过 PSMG3 增强宿主细胞的 UPS、自噬和抗凋亡
DOI：
10.1016/j.ijbiomac.2021.06.039
复制
发表时间：
2021-06-24
影响因子：
8.2
通讯作者：
Chen, Chuangfu
中科院分区：
文献类型：
--
作者：
Ma, Zhongchen;Li, Ruirui;Chen, Chuangfu
嗜吞噬细胞无原体是一种专性细胞内细菌，是一种常见的蜱传感染性病原体，可引起人粒细胞无原体病（HGA）。效应蛋白在嗜吞噬单胞菌的致病机制中起重要作用，但具体的发病机制尚不清楚。我们利用酵母双杂交法对效应蛋白AptA （A. phagocytophilum toxin A）进行筛选，筛选其相互作用蛋白蛋白酶体组装伴侣蛋白3 (PSMG3, PAC3)，并确定了A. phagocytophilum在HEK293T细胞中的致病性新机制。AptA进入宿主细胞后，与PSMG3相互作用增强蛋白酶体活性，引起宿主细胞泛素化和自噬，从而增加泛素化-蛋白酶体系统（ubiquitination-proteasome system， UPS）与自噬之间的串扰。AptA还能降低宿主细胞的凋亡效率。这些结果为探讨嗜吞噬细胞芽孢杆菌的致病机制提供了新的线索，并支持了AptA与宿主PSMG3相互作用的假说。
Anaplasma phagocytophilum is an obligate intracellular bacterium and a common tick-borne infectious pathogen that can cause human granulocytic anaplasmosis (HGA). Effector proteins play an important role in the pathogenic mechanism of A. phagocytophilum, but the specifics of the disease mechanism are unclear. We studied the effector protein AptA (A. phagocytophilum toxin A) using yeast two hybrid assays to screen its interacting protein proteasome assembly chaperone 3 (PSMG3, PAC3), and identified new mechanisms for the pathogenicity of A. phagocytophilum in HEK293T cells. After AptA enters the host cell, it interacts with PSMG3 to enhance the activity of the proteasome, causing ubiquitination and autophagy in the host cell and thereby increasing crosstalk between the ubiquitination-proteasome system (UPS) and autophagy. AptA also reduces the apoptotic efficiency of the host cells. These results offer new clues as to the pathogenic mechanism of A. phagocytophilum and support the hypothesis that AptA interacts with host PSMG3.