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 Tooze; Muriel C Mari; Terje Johansen; Fulvio Reggiori; Vojo Deretic

doi:10.1038/s41556-021-00706-w

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 journal › Article › Academic › peer-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 language	English
Pages (from-to)	846–858
Number of pages	36
Journal	Nature Cell Biology
Volume	23
Issue number	8
DOIs	https://doi.org/10.1038/s41556-021-00706-w
Publication status	Published - Aug-2021

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Claude-Taupin, A., Jia, J., Bhujabal, Z., Garfa-Traoré, M., Kumar, S., da Silva, G. P. D., Javed, R., Gu, Y., Allers, L., Peters, R., Wang, F., da Costa, L. J., Pallikkuth, S., Lidke, K. A., Mauthe, M., Verlhac, P., Uchiyama, Y., Salemi, M., Phinney, B., ... Deretic, V. (2021). ATG9A protects the plasma membrane from programmed and incidental permeabilization. Nature Cell Biology, 23(8), 846–858. https://doi.org/10.1038/s41556-021-00706-w

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title = "ATG9A protects the plasma membrane from programmed and incidental permeabilization",

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.",

author = "Aurore Claude-Taupin and Jingyue Jia and Zambarlal Bhujabal and Meriem Garfa-Traor{\'e} and Suresh Kumar and {da Silva}, {Gustavo Peixoto Duarte} and Ruheena Javed and Yuexi Gu and Lee Allers and Ryan Peters and Fulong Wang and {da Costa}, {Luciana Jesus} and Sandeep Pallikkuth and Lidke, {Keith A} and Mario Mauthe and Pauline Verlhac and Yasuo Uchiyama and Michelle Salemi and Brett Phinney and Tooze, {Sharon A} and Mari, {Muriel C} and Terje Johansen and Fulvio Reggiori and Vojo Deretic",

note = "{\textcopyright} 2021. The Author(s), under exclusive licence to Springer Nature Limited.",

year = "2021",

month = aug,

doi = "10.1038/s41556-021-00706-w",

language = "English",

volume = "23",

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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 2021, 'ATG9A protects the plasma membrane from programmed and incidental permeabilization', Nature Cell Biology, vol. 23, no. 8, pp. 846–858. https://doi.org/10.1038/s41556-021-00706-w

TY - JOUR

T1 - ATG9A protects the plasma membrane from programmed and incidental permeabilization

AU - Claude-Taupin, Aurore

AU - Jia, Jingyue

AU - Bhujabal, Zambarlal

AU - Garfa-Traoré, Meriem

AU - Kumar, Suresh

AU - da Silva, Gustavo Peixoto Duarte

AU - Javed, Ruheena

AU - Gu, Yuexi

AU - Allers, Lee

AU - Peters, Ryan

AU - Wang, Fulong

AU - da Costa, Luciana Jesus

AU - Pallikkuth, Sandeep

AU - Lidke, Keith A

AU - Mauthe, Mario

AU - Verlhac, Pauline

AU - Uchiyama, Yasuo

AU - Salemi, Michelle

AU - Phinney, Brett

AU - Tooze, Sharon A

AU - Mari, Muriel C

AU - Johansen, Terje

AU - Reggiori, Fulvio

AU - Deretic, Vojo

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

U2 - 10.1038/s41556-021-00706-w

DO - 10.1038/s41556-021-00706-w

M3 - Article

C2 - 34257406

SN - 1465-7392

VL - 23

SP - 846

EP - 858

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 8

ER -