Reference - Detail
| RRC ID | 73639 |
|---|---|
| Author | Jiang P, Nishimura T, Sakamaki Y, Itakura E, Hatta T, Natsume T, Mizushima N. |
| Title | The HOPS complex mediates autophagosome-lysosome fusion through interaction with syntaxin 17. |
| Journal | Mol Biol Cell |
| Abstract |
Membrane fusion is generally controlled by Rabs, soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs), and tethering complexes. Syntaxin 17 (STX17) was recently identified as the autophagosomal SNARE required for autophagosome-lysosome fusion in mammals and Drosophila. In this study, to better understand the mechanism of autophagosome-lysosome fusion, we searched for STX17-interacting proteins. Immunoprecipitation and mass spectrometry analysis identified vacuolar protein sorting 33A (VPS33A) and VPS16, which are components of the homotypic fusion and protein sorting (HOPS)-tethering complex. We further confirmed that all HOPS components were coprecipitated with STX17. Knockdown of VPS33A, VPS16, or VPS39 blocked autophagic flux and caused accumulation of STX17- and microtubule-associated protein light chain (LC3)-positive autophagosomes. The endocytic pathway was also affected by knockdown of VPS33A, as previously reported, but not by knockdown of STX17. By contrast, ultraviolet irradiation resistance-associated gene (UVRAG), a known HOPS-interacting protein, did not interact with the STX17-HOPS complex and may not be directly involved in autophagosome-lysosome fusion. Collectively these results suggest that, in addition to its well-established function in the endocytic pathway, HOPS promotes autophagosome-lysosome fusion through interaction with STX17. |
| Volume | 25(8) |
| Pages | 1327-37 |
| Published | 2014-4-1 |
| DOI | 10.1091/mbc.E13-08-0447 |
| PII | mbc.E13-08-0447 |
| PMID | 24554770 |
| PMC | PMC3982997 |
| MeSH | Animals Autophagy-Related Proteins Cell Fusion Green Fluorescent Proteins / genetics HEK293 Cells HeLa Cells Humans Intracellular Signaling Peptides and Proteins / genetics Lysosomes / immunology* Membrane Fusion / genetics Membrane Fusion / physiology* Mice Microtubule-Associated Proteins / metabolism Oligopeptides / immunology Phagosomes / immunology* Protein Binding Qa-SNARE Proteins / genetics Qa-SNARE Proteins / metabolism* RNA Interference RNA, Small Interfering Tumor Suppressor Proteins / metabolism Vesicular Transport Proteins / genetics Vesicular Transport Proteins / metabolism* |
| IF | 3.791 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 8 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| DNA material | pMXsIP-GFP-VPS33A (RDB19783) pMRXIP-VPS16-GFP (RDB19787) |