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Nat Cell Biol. 2014 Dec;16(12):1215-26. doi: 10.1038/ncb3066. Epub 2014 Nov 24.

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

Author information

1
State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
2
National Institute of Biological Sciences, Beijing 102206, China.
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.
4
Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest 1117, Hungary.

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.

PMID:
25419848
DOI:
10.1038/ncb3066
[Indexed for MEDLINE]

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