Cell
Volume 151, Issue 6, 7 December 2012, Pages 1256-1269
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Article
The Hairpin-type Tail-Anchored SNARE Syntaxin 17 Targets to Autophagosomes for Fusion with Endosomes/Lysosomes

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Summary

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.

Highlights

► Syntaxin 17 is present on completed autophagosomes but not isolation membranes ► Stx17 is required for autophagosomal fusion with the endosome/lysosome ► Stx17 has two tandem transmembrane domains containing glycine zipper-like motifs ► The hairpin-like transmembrane structure is required for autophagosomal targeting

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2

Present address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge CB2 0QH, UK

3

Present address: Department of Biochemistry and Molecular Biology, Graduate School and Faculty of Medicine, The University of Tokyo, Tokyo 113-0033, Japan