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Mammalian Atg8 proteins regulate lysosome and autolysosome biogenesis through SNAREs


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 broadens 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 remodelling in eukaryotic cells and expand the roles of mAtg8s to lysosome biogenesis.

SUBMITTER: Yuexi Gu 

PROVIDER: S-SCDT-EMBOJ-2019-101994 | biostudies-other |

REPOSITORIES: biostudies-other

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