ATG9A protects the plasma membrane from programmed and incidental permeabilization.

ATG9A protects the plasma membrane from programmed and incidental permeabilization.
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DOI:
10.1038/s41556-021-00706-w
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发表时间:
2021-08
影响因子:
21.3
通讯作者:
Deretic V
Deretic V
中科院分区:
生物学1区
文献类型:
--
作者:
Claude-Taupin A;Jia J;Bhujabal Z;Garfa-Traoré M;Kumar S;da Silva GPD;Javed R;Gu Y;Allers L;Peters R;Wang F;da Costa LJ;Pallikkuth S;Lidke KA;Mauthe M;Verlhac P;Uchiyama Y;Salemi M;Phinney B;Tooze SA;Mari MC;Johansen T;Reggiori F;Deretic V

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整合膜蛋白ATG 9A在自噬中起关键作用。它显示出广泛的细胞内分布,并存在于许多隔室中,包括质膜(PM)。ATG 9A分配给PM的原因及其在PM中的作用尚不清楚。在这里,我们表明,ATG 9A组织,与IQGAP 1,ESCRT系统的组成部分,并发现ATG 9A,IQGAP 1和ESCRT之间的合作,在保护PM损害。ESCRT和ATG 9A表型相互模仿,以防止PM损伤。ATG 9A敲除使PM对广谱微生物和内源性试剂(包括gasdermin、MLKL和冠状病毒ORF 3a的MLKL样作用)的透化敏感。因此,ATG 9A与IQGAP 1和ESCRT系统接合,以保持PM完整性。Claude-Taupin等人表明,ATG 9A通过涉及IQGAP 1和ESCRT的机制介导在不同生物学环境中对质膜损伤的保护。
The integral membrane protein ATG9A plays a key role in autophagy. It displays a broad intracellular distribution and is present in numerous compartments, including the plasma membrane (PM). The reasons for the distribution of ATG9A to the PM and its role at the PM are not understood. Here, we show that ATG9A organizes, in concert with IQGAP1, components of the ESCRT system and uncover cooperation between ATG9A, IQGAP1 and ESCRTs in protection from PM damage. ESCRTs and ATG9A phenocopied each other in protection against PM injury. ATG9A knockouts sensitized the PM to permeabilization by a broad spectrum of microbial and endogenous agents, including gasdermin, MLKL and the MLKL-like action of coronavirus ORF3a. Thus, ATG9A engages IQGAP1 and the ESCRT system to maintain PM integrity. Claude-Taupin et al. show that ATG9A mediates protection against plasma membrane damage in diverse biological contexts through a mechanism involving IQGAP1 and ESCRTs.
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