ATG9A protects the plasma membrane from programmed and incidental permeabilization,Nature Cell Biology

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ATG9A protects the plasma membrane from programmed and incidental permeabilization
Nature Cell Biology ( IF 17.3 ) Pub Date : 2021-07-12 , DOI: 10.1038/s41556-021-00706-w
Aurore Claude-Taupin _{1,

2} , Jingyue Jia _{1,

2} , Zambarlal Bhujabal ₃ , Meriem Garfa-Traoré ₄ , 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 Costa ₅ , Sandeep Pallikkuth ₆ , Keith A Lidke ₆ , Mario Mauthe ₇ , Pauline Verlhac ₇ , Yasuo Uchiyama ₈ , Michelle Salemi ₉ , Brett Phinney ₉ , Sharon A Tooze ₁₀ , Muriel C Mari ₇ , Terje Johansen ₃ , Fulvio Reggiori ₇ , Vojo Deretic _{1,

2}

Affiliation

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

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.

中文翻译：

ATG9A 保护质膜免受程序性和意外的透化作用

整合膜蛋白 ATG9A 在自噬中发挥着关键作用。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)。将 ATG9A 分配给 PM 的原因及其在 PM 中的作用尚不清楚。在这里，我们展示了 ATG9A 与 IQGAP1 协同组织 ESCRT 系统的组件，并揭示了 ATG9A、IQGAP1 和 ESCRT 之间在防止 PM 损坏方面的合作。 ESCRT 和 ATG9A 彼此相似，可防止 PM 损伤。 ATG9A 敲除使 PM 对多种微生物和内源性物质的透化敏感，包括 Gasdermin、MLKL 和冠状病毒 ORF3a 的 MLKL 样作用。因此，ATG9A 结合 IQGAP1 和 ESCRT 系统来维持 PM 完整性。

更新日期：2021-07-12

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