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

Nature Cell Biology volume 16, pages 12151226 (2014) | Download Citation

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.

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Acknowledgements

We thank I. Hanson for editing services and F. Shao (NIBS) for OGA proteins. Some strains were obtained from CGC, which is funded by the National Institutes of Health (P40 OD010440). This work was supported by the National Basic Research Program of China (2013CB910100, 2011CB910100) and also a grant from the National Natural Science Foundation of China (31225018) to H.Z. The research of H.Z. was supported in part by an International Early Career Scientist grant from the Howard Hughes Medical Institute.

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Author notes

    • Bin Guo
    •  & Qianqian Liang

    These authors contributed equally to this work.

Affiliations

  1. State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China

    • Bin Guo
    • , Qianqian Liang
    • , Fan Wu
    • , Peipei Zhang
    •  & Hong Zhang
  2. National Institute of Biological Sciences, Beijing 102206, China

    • Lin Li
    • , Yongfen Ma
    • , Zhiyuan Zhang
    •  & She Chen
  3. Institute of Neurology, Key Laboratory of Age-Associated Cardiac-Cerebral Vascular Disease of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China

    • Zhe Hu
    • , Bin Zhao
    •  & Du Feng
  4. Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest 1117, Hungary

    • Attila L. Kovács

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Contributions

B.G., D.F., Z.Z., S.C. and H.Z. designed the experiments. B.G., Q.L., L.L., Z.H., P.Z., F.W., Y.M. and B.Z. performed the experiments. A.L.K. and D.F. analysed the electron micrographs. B.G., S.C. and H.Z. wrote the manuscript.

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The authors declare no competing financial interests.

Corresponding author

Correspondence to Hong Zhang.

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https://doi.org/10.1038/ncb3066

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