Reference - Detail
| RRC ID | 45736 |
|---|---|
| Author | Guo B, Liang Q, Li L, Hu Z, Wu F, Zhang P, Ma Y, Zhao B, Kovács AL, Zhang Z, Feng D, Chen S, Zhang H. |
| Title | O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. |
| Journal | Nat Cell Biol |
| Abstract |
The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. Here, we report that O-linked β-N-acetylglucosamine (O-GlcNAc) transferase (OGT) mediates O-GlcNAcylation of the SNARE protein SNAP-29 and regulates autophagy in a nutrient-dependent manner. In mammalian cells, OGT knockdown, or mutating the O-GlcNAc sites in SNAP-29, promotes the formation of a SNAP-29-containing SNARE complex, increases fusion between autophagosomes and endosomes/lysosomes, and promotes autophagic flux. In Caenorhabditis elegans, depletion of ogt-1 has a similar effect on autophagy; moreover, expression of an O-GlcNAc-defective SNAP-29 mutant facilitates autophagic degradation of protein aggregates. O-GlcNAcylated SNAP-29 levels are reduced during starvation in mammalian cells and in C. elegans. Our study reveals a mechanism by which O-GlcNAc-modification integrates nutrient status with autophagosome maturation. |
| Volume | 16(12) |
| Pages | 1215-26 |
| Published | 2014-12-1 |
| DOI | 10.1038/ncb3066 |
| PII | ncb3066 |
| PMID | 25419848 |
| MeSH | Acetylglucosamine / metabolism* Animals Autophagy / physiology* Autophagy-Related Proteins Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Endosomes / physiology* Green Fluorescent Proteins / genetics HeLa Cells Humans Lysosome-Associated Membrane Glycoproteins Lysosomes / physiology* Membrane Fusion* Mutation N-Acetylglucosaminyltransferases / genetics N-Acetylglucosaminyltransferases / metabolism* Phagosomes / physiology* Protein Binding Proteins / genetics Q-SNARE Proteins / genetics Q-SNARE Proteins / metabolism Qa-SNARE Proteins / genetics Qb-SNARE Proteins / genetics Qb-SNARE Proteins / metabolism* Qc-SNARE Proteins / genetics Qc-SNARE Proteins / metabolism* R-SNARE Proteins / genetics RNA Interference RNA, Small Interfering Signal Transduction / genetics Vesicular Transport Proteins |
| IF | 20.042 |
| Times Cited | 116 |
| WOS Category | CELL BIOLOGY |
| Resource | |
| C.elegans | tm3425 tm1036 tm1046 |