title: The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes.
abstract: The lysosome is a degradative organelle, and its fusion with other organelles is strictly regulated. In contrast to fusion with the late endosome, the mechanisms underlying autophagosome-lysosome fusion remain unknown. Here, we identify syntaxin 17 (Stx17) as the autophagosomal SNARE required for fusion with the endosome/lysosome. Stx17 localizes to the outer membrane of completed autophagosomes but not to the isolation membrane (unclosed intermediate structures); for this reason, the lysosome does not fuse with the isolation membrane. Stx17 interacts with SNAP-29 and the endosomal/lysosomal SNARE VAMP8. Depletion of Stx17 causes accumulation of autophagosomes without degradation. Stx17 has a unique C-terminal hairpin structure mediated by two tandem transmembrane domains containing glycine zipper-like motifs, which is essential for its association with the autophagosomal membrane. These findings reveal a mechanism by which the SNARE protein is available to the completed autophagosome.
authors.affiliation: Department of Physiology and Cell Biology, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
authors.forename: Eisuke
authors.initials: E
authors.lastname: Itakura
authors.forename: Chieko
authors.initials: C
authors.lastname: Kishi-Itakura
authors.forename: Noboru
authors.initials: N
authors.lastname: Mizushima
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001343:Autophagy; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010588:Phagosomes / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D050765:Qa-SNARE Proteins / Q000737:chemistry / Q000378:metabolism*; D016415:Sequence Alignment
chemical_list: D050765:Qa-SNARE Proteins; C551267:STX17 protein, human; C578013:Stx17 protein, mouse