Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs.

FULLTEXT
Published:
10.19.2019
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Last Revised:
10.18.2019
PMID:
31625181
The EMBO journal
Journal Article
Authors:
Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical 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.
Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical 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.
Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical 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.
Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical 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.
Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.
Institute of Biomedicine, University of Turku, Turku, Finland.
Molecular Cancer Research Group, Institute of Medical Biology, University of Tromsø-The Arctic University of Norway, Tromsø, Norway.
Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical 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.

Abstract

Mammalian homologs of yeast Atg8 protein (mAtg8s) are important in autophagy, but their exact mode of action remains ill-defined. Syntaxin 17 (Stx17), a SNARE with major roles in autophagy, was recently shown to bind mAtg8s. Here, we identified LC3-interacting regions (LIRs) in several SNAREs that broaden the landscape of the mAtg8-SNARE interactions. We found that Syntaxin 16 (Stx16) and its cognate SNARE partners all have LIR motifs and bind mAtg8s. Knockout of Stx16 caused defects in lysosome biogenesis, whereas a Stx16 and Stx17 double knockout completely blocked autophagic flux and decreased mitophagy, pexophagy, xenophagy, and ribophagy. Mechanistic analyses revealed that mAtg8s and Stx16 control several properties of lysosomal compartments including their function as platforms for active mTOR. These findings reveal a broad direct interaction of mAtg8s with SNAREs with impact on membrane remodeling in eukaryotic cells and expand the roles of mAtg8s to lysosome biogenesis.

GrantID: R37AI042999, Agency: HHS|NIH|National Institute of Allergy and Infectious Diseases (NIAID), Country: Array | GrantID: R01AI042999, Agency: HHS|NIH|National Institute of Allergy and Infectious Diseases (NIAID), Country: Array | GrantID: P20GM121176, Agency: HHS|NIH|National Institute of General Medical Sciences (NIGMS), Country: Array | GrantID: FT1601100063, Agency: ARC Future Fellowship, Country: Array | GrantID: GNT1106471, Agency: Department of Health|National Health and Medical Research Council (NHMRC), Country: Array | GrantID: GNT1160315, Agency: Department of Health|National Health and Medical Research Council (NHMRC), Country: Array | GrantID: 190214, Agency: Norwegian Cancer Society, Country: Array | GrantID: 249884, Agency: Research Council of Norway, Country: Array
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