O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation
Author: ["Bin Guo","Qianqian Liang","Lin Li","Zhe Hu","Fan Wu","Peipei Zhang","Yongfen Ma","Bin Zhao","Attila L. Kovács","Zhiyuan Zhang","Du Feng","She Chen","Hong Zhang"]
Publication: Nature Cell Biology
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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. Zhang and colleagues report that starvation reduces O-GlcNAcylation of the SNARE protein SNAP-29. This promotes formation of a competent SNARE complex that increases autophagosome–lysosome fusion, increasing autophagosome maturation and flux.
Cite this article
Guo, B., Liang, Q., Li, L. et al. O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nat Cell Biol 16, 1215–1226 (2014). https://doi.org/10.1038/ncb3066
