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

Nat Cell Biol. 2021 Aug;23(8):846-858. doi: 10.1038/s41556-021-00706-w. Epub 2021 Jul 12.

Authors

Aurore Claude-Taupin^{1

2}, Jingyue Jia^{1

2}, Zambarlal Bhujabal³, Meriem Garfa-Traoré⁴, Suresh Kumar^{1

2}, Gustavo Peixoto Duarte da Silva^{1

2

5}, Ruheena Javed^{1

2}, Yuexi Gu^{1

2}, Lee Allers^{1

2}, Ryan Peters^{1

2}, Fulong Wang^{1

2}, Luciana Jesus da Costa⁵, Sandeep Pallikkuth⁶, Keith A Lidke⁶, Mario Mauthe⁷, Pauline Verlhac⁷, Yasuo Uchiyama⁸, Michelle Salemi⁹, Brett Phinney⁹, Sharon A Tooze¹⁰, Muriel C Mari⁷, Terje Johansen³, Fulvio Reggiori⁷, Vojo Deretic^{11

12}

Affiliations

¹ Autophagy, Inflammation and Metabolic (AIM) Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
² Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
³ Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
⁴ Cell Imaging Platform, INSERM US24 Structure Fédérative de Recherche Necker, Université de Paris, Paris, France.
⁵ Departamento de Virologia, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
⁶ Department of Physics and Astronomy, University of New Mexico, Albuquerque, NM, USA.
⁷ Department of Biomedical Sciences of Cells and Systems, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
⁸ Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
⁹ Proteomics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, CA, USA.
¹⁰ The Francis Crick Institute, Molecular Cell Biology of Autophagy Laboratory, London, UK.
¹¹ Autophagy, Inflammation and Metabolic (AIM) Center of Biochemical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. vderetic@salud.unm.edu.
¹² Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. vderetic@salud.unm.edu.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Autophagosomes / metabolism
Autophagy-Related Proteins / genetics
Autophagy-Related Proteins / metabolism*
Cell Membrane / metabolism*
HEK293 Cells
HeLa Cells
Humans
Immunoblotting
Immunoprecipitation
Membrane Proteins / genetics
Membrane Proteins / metabolism*
Microscopy, Confocal
Protein Transport / physiology
Vesicular Transport Proteins / genetics
Vesicular Transport Proteins / metabolism*

Substances

ATG9A protein, human
Autophagy-Related Proteins
Membrane Proteins
Vesicular Transport Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding