Reference - Detail
| 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 |
| IF | 38.637 |
| Resource | |
| DNA material | pMRX-IP-GFP-STX17 (RDB19636) pMRX-IP-GFP-SNAP29 (RDB19638) pMRX-IP-GFP-VAMP7 (RDB19639) pMRX-IP-GFP-VAMP8 (RDB19640) p3xFLAG-CMV10-Stx17 (RDB19761) p3xFLAG-CMV10-SNAP29 (RDB19765) p3xFLAG-CMV10-VAMP7 (RDB19778) pMRXIP GFP-Stx7 (RDB19779) pMRXIP-GFP-Stx18 (RDB19792) pMRXIP-GFP-Stx17TM (RDB19793) |