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ATG5 provides host protection acting as a switch in the atg8ylation cascade between autophagy and secretion.
Wang, Fulong; Peters, Ryan; Jia, Jingyue; Mudd, Michal; Salemi, Michelle; Allers, Lee; Javed, Ruheena; Duque, Thabata L A; Paddar, Masroor A; Trosdal, Einar S; Phinney, Brett; Deretic, Vojo.
Afiliación
  • Wang F; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Peters R; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Jia J; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Mudd M; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Salemi M; Proteomics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA.
  • Allers L; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Javed R; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Duque TLA; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Paddar MA; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Trosdal ES; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
  • Phinney B; Proteomics Core Facility, UC Davis Genome Center, University of California, Davis, Davis, CA 95616, USA.
  • Deretic V; Autophagy, Inflammation and Metabolism Center of Biochemical Research Excellence, University of New Mexico School of Medicine, 915 Camino de Salud, NE, Albuquerque, NM 87131, USA; Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, 915 Camino de Salud, NE,
Dev Cell ; 58(10): 866-884.e8, 2023 05 22.
Article en En | MEDLINE | ID: mdl-37054706
ATG5 is a part of the E3 ligase directing lipidation of ATG8 proteins, a process central to membrane atg8ylation and canonical autophagy. Loss of Atg5 in myeloid cells causes early mortality in murine models of tuberculosis. This in vivo phenotype is specific to ATG5. Here, we show using human cell lines that absence of ATG5, but not of other ATGs directing canonical autophagy, promotes lysosomal exocytosis and secretion of extracellular vesicles and, in murine Atg5fl/fl LysM-Cre neutrophils, their excessive degranulation. This is due to lysosomal disrepair in ATG5 knockout cells and the sequestration by an alternative conjugation complex, ATG12-ATG3, of ESCRT protein ALIX, which acts in membrane repair and exosome secretion. These findings reveal a previously undescribed function of ATG5 in its host-protective role in murine experimental models of tuberculosis and emphasize the significance of the branching aspects of the atg8ylation conjugation cascade beyond the canonical autophagy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Proteínas Asociadas a Microtúbulos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Proteínas Asociadas a Microtúbulos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Dev Cell Asunto de la revista: EMBRIOLOGIA Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos