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, A. Kovács, Zhiyuan Zhang, Du Feng, She Chen, Hong Zhang

Research output: Contribution to journalArticle

103 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

Fingerprint

SNARE Proteins
Endosomes
Autophagy
Lysosomes
Food
Acetylglucosamine
Caenorhabditis elegans
Starvation
Autophagosomes
O-GlcNAc transferase
Protein Aggregates

ASJC Scopus subject areas

  • Cell Biology
  • Medicine(all)

Cite this

Guo, B., Liang, Q., Li, L., Hu, Z., Wu, F., Zhang, P., ... 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

O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. / Guo, Bin; Liang, Qianqian; Li, Lin; Hu, Zhe; Wu, Fan; Zhang, Peipei; Ma, Yongfen; Zhao, Bin; Kovács, A.; Zhang, Zhiyuan; Feng, Du; Chen, She; Zhang, Hong.

In: Nature Cell Biology, Vol. 16, No. 12, 01.12.2014, p. 1215-1226.

Research output: Contribution to journalArticle

Guo, B, Liang, Q, Li, L, Hu, Z, Wu, F, Zhang, P, Ma, Y, Zhao, B, Kovács, A, Zhang, Z, Feng, D, Chen, S & Zhang, H 2014, 'O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation', Nature Cell Biology, vol. 16, no. 12, pp. 1215-1226. https://doi.org/10.1038/ncb3066
Guo B, Liang Q, Li L, Hu Z, Wu F, Zhang P et al. O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. Nature Cell Biology. 2014 Dec 1;16(12):1215-1226. https://doi.org/10.1038/ncb3066
Guo, Bin ; Liang, Qianqian ; Li, Lin ; Hu, Zhe ; Wu, Fan ; Zhang, Peipei ; Ma, Yongfen ; Zhao, Bin ; Kovács, A. ; Zhang, Zhiyuan ; Feng, Du ; Chen, She ; Zhang, Hong. / O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation. In: Nature Cell Biology. 2014 ; Vol. 16, No. 12. pp. 1215-1226.
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