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ATG9A protects the plasma membrane from programmed and incidental permeabilization.

Nature cell biology (2021-07-15)
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 Tooze, Muriel C Mari, Terje Johansen, Fulvio Reggiori, Vojo Deretic
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.

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