最新重要论文(影响因子PNAS及以上)

A Bacterial Effector Reveals the V-ATPase-ATG16L1 Axis that Initiates Xenophagy, Cell, 25 Jul 2019

发布时间:2019年07月25日

Cell25 July, 2019,DOI:https://doi.org/10.1016/j.cell.2019.06.007

A Bacterial Effector Reveals the V-ATPase-ATG16L1 Axis that Initiates Xenophagy

Yue Xu, Ping Zhou, Sen Cheng, Qiuhe Lu, Kathrin Nowak, Ann-Katrin Hopp, Lin Li, Xuyan Shi, Zhiwei Zhou, Wenqing Gao, Da Li, Huabin He, Xiaoyun Liu, Jingjin Ding, Michael O. Hottiger, Feng Shao

Abstract

Antibacterial autophagy (xenophagy) is an important host defense, but how it is initiated is unclear. Here, we performed a bacterial transposon screen and identified a T3SS effector SopF that potently blocked Salmonella autophagy. SopF was a general xenophagy inhibitor without affecting canonical autophagy. S. Typhimurium ΔsopF resembled S. flexneri ΔvirAΔicsB with the majority of intracellular bacteria targeted by autophagy, permitting a CRISPR screen that identified host V-ATPase as an essential factor. Upon bacteria-caused vacuolar damage, the V-ATPase recruited ATG16L1 onto bacteria-containing vacuole, which was blocked by SopF. Mammalian ATG16L1 bears a WD40 domain required for interacting with the V-ATPase. Inhibiting autophagy by SopF promoted S. Typhimurium proliferation in vivo. SopF targeted Gln124 of ATP6V0C in the V-ATPase for ADP-ribosylation. Mutation of Gln124 also blocked xenophagy, but not canonical autophagy. Thus, the discovery of SopF reveals the V-ATPase-ATG16L1 axis that critically mediates autophagic recognition of intracellular pathogen.

文章链接:https://www.sciencedirect.com/science/article/pii/S009286741930635X?via%3Dihub

 

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