ATG9A protects the plasma membrane from programmed and incidental permeabilization

Aurore Claude-Taupin, Jingyue Jia, Zambarlal Bhujabal, Meriem Garfa-Traoré, Suresh Kumar, Gustavo Peixoto Duarte da Silva, Ruheena Javed, Yuexi Gu, Lee Allers, Ryan Peters, Fulong Wang, Luciana Jesus da Costa, Sandeep Pallikkuth, Keith A Lidke, Mario Mauthe, Pauline Verlhac, Yasuo Uchiyama, Michelle Salemi, Brett Phinney, Sharon A ToozeMuriel C Mari, Terje Johansen, Fulvio Reggiori, Vojo Deretic*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Pages (from-to)846–858
Number of pages36
JournalNature Cell Biology
Volume23
Issue number8
DOIs
Publication statusPublished - Aug-2021

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