O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation, Nature Cell Biology, Published online 24 November 2014
发布时间：2014年11月26日
Nature Cell Biology, Published online 24 November 2014 , DOI: doi:10.1038/ncb3066
O-GlcNAc-modification of ？SNAP-29 regulates autophagosome maturation
Bin Guo,1, n1 Qianqian Liang,1, n1 Lin Li,2, Zhe Hu,3, Fan Wu,1, Peipei Zhang,1, Yongfen Ma,2, Bin Zhao,3, Attila L. Kovács,4, Zhiyuan Zhang,2, Du Feng,3, She Chen2, & Hong Zhang1,
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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O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation, Nature Cell Biology, Published online 24 November 2014
Nature Cell Biology, Published online 24 November 2014 , DOI: doi:10.1038/ncb3066
O-GlcNAc-modification of ？SNAP-29 regulates autophagosome maturation
Bin Guo,1, n1 Qianqian Liang,1, n1 Lin Li,2, Zhe Hu,3, Fan Wu,1, Peipei Zhang,1, Yongfen Ma,2, Bin Zhao,3, Attila L. Kovács,4, Zhiyuan Zhang,2, Du Feng,3, She Chen2, & Hong Zhang1,
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.
相关报道：http://www.ibp.cas.cn/kyjz/zxdt/201411/t20141126_4261313.html
文章链接：http://www.nature.com/ncb/journal/vaop/ncurrent/full/ncb3066.html