Mammalian hybrid pre-autophagosomal structure HyPAS generates autophagosomes
Autor: | Jing Li, Jan Haug Anonsen, Eeva-Liisa Eskelinen, Sigurdur Gudmundsson, Suresh Kumar, Vojo Deretic, Chunyan Ye, Brett S. Phinney, Sandeep Pallikkuth, Keith A. Lidke, Alf Håkon Lystad, Graham S. Timmins, Tor Erik Rusten, Anne Simonsen, Steven B. Bradfute, Michelle Salemi, Ashish Jain, Michal H. Mudd, Aurore Claude-Taupin, Karthikeyan Tangavelou, Ruheena Javed, Lian-Wang Guo |
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Jazyk: | angličtina |
Rok vydání: | 2021 |
Předmět: |
coronavirus
sigma ATG16L1 Golgi Apparatus Endoplasmic Reticulum Medical and Health Sciences Membrane Fusion Synaptotagmins Phagosomes Receptors Golgi Lung Microscopy Tumor Microscopy Confocal Qa-SNARE Proteins Vesicle Biological Sciences Cell biology Infectious Diseases Membrane Confocal symbols autophagy Endosome Endosomes Syntaxin 17 Biology General Biochemistry Genetics and Molecular Biology Article Cell Line Sarcoplasmic Reticulum Calcium-Transporting ATPases Vaccine Related Atg8ylation symbols.namesake Biodefense Cell Line Tumor Autophagy Humans Receptors sigma FIP200 endosome Pre-autophagosomal structure SARS-CoV-2 Prevention Autophagosomes Lipid bilayer fusion COVID-19 Pneumonia Golgi apparatus Emerging Infectious Diseases HEK293 Cells Hela Cells CRISPR-Cas Systems Biogenesis Developmental Biology HeLa Cells |
Zdroj: | Cell Cell, vol 184, iss 24 |
Popis: | The biogenesis of mammalian autophagosomes remains to be fully defined. Here, we used cellular and invitro membrane fusion analyses to show that autophagosomes are formed from a hitherto unappreciated hybrid membrane compartment. The autophagic precursors emerge through fusion of FIP200 vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes to generate a hybrid pre-autophagosomal structure, HyPAS. A previously unrecognized apparatus defined here controls HyPAS biogenesis and mammalian autophagosomal precursor membranes. HyPAS can be modulated by pharmacological agents whereas its formation is inhibited upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or by expression of SARS-CoV-2nsp6. These findings reveal the origin of mammalian autophagosomal membranes, which emerge via convergence of secretory and endosomal pathways, and show that this process is targeted by microbial factors such as coronaviral membrane-modulating proteins. |
Databáze: | OpenAIRE |
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