O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation

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

Research output: Article

115 Citations (Scopus)

Abstract

The mechanism by which nutrient status regulates the fusion of autophagosomes with endosomes/lysosomes is poorly understood. Here, we report that O-linked 2-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.

Original languageEnglish
Pages (from-to)1215-1226
Number of pages12
JournalNature Cell Biology
Volume16
Issue number12
DOIs
Publication statusPublished - dec. 1 2014

ASJC Scopus subject areas

  • Cell Biology

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    Guo, B., Liang, Q., Li, L., Hu, Z., Wu, F., Zhang, P., Ma, Y., Zhao, B., Kovács, A. L., Zhang, Z., Feng, D., Chen, S., & Zhang, H. (2014). O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nature Cell Biology, 16(12), 1215-1226. https://doi.org/10.1038/ncb3066