RRC ID 72410
Author Itakura E, Kishi-Itakura C, Mizushima N.
Title The hairpin-type tail-anchored SNARE syntaxin 17 targets to autophagosomes for fusion with endosomes/lysosomes.
Journal Cell
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.
Volume 151(6)
Pages 1256-69
Published 2012-12-7
DOI 10.1016/j.cell.2012.11.001
PII S0092-8674(12)01336-0
PMID 23217709
MeSH Amino Acid Motifs Amino Acid Sequence Animals Autophagy Cell Line Cytosol / metabolism Endosomes / metabolism* Fibroblasts / metabolism HEK293 Cells HeLa Cells Humans Lysosomes / metabolism* Mice Molecular Sequence Data Phagosomes / metabolism* Protein Structure, Tertiary Qa-SNARE Proteins / chemistry Qa-SNARE Proteins / metabolism* Sequence Alignment
Resource
DNA material pMRX-IP-GFP-STX17 (RDB19636) pMRX-IP-GFP-SNAP29 (RDB19638) pMRX-IP-GFP-VAMP7 (RDB19639) pMRX-IP-GFP-VAMP8 (RDB19640)