title: O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation.
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.
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Liang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Neurology, Key Laboratory of Age-Associated Cardiac-Cerebral Vascular Disease of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Yongfen
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Institute of Neurology, Key Laboratory of Age-Associated Cardiac-Cerebral Vascular Disease of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.affiliation: Department of Anatomy, Cell and Developmental Biology, Eötvös Loránd University, Budapest 1117, Hungary.
authors.forename: Attila L
authors.initials: AL
authors.lastname: Kovács
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Institute of Neurology, Key Laboratory of Age-Associated Cardiac-Cerebral Vascular Disease of Guangdong Province, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
authors.forename: Du
authors.initials: D
authors.lastname: Feng
authors.affiliation: National Institute of Biological Sciences, Beijing 102206, China.
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000818:Animals; D001343:Autophagy / Q000502:physiology*; D000071183:Autophagy-Related Proteins; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D051907:Lysosomal Membrane Proteins; D008247:Lysosomes / Q000502:physiology*; D008561:Membrane Fusion; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000502:physiology*; D011485:Protein Binding; D011506:Proteins / Q000235:genetics; D050682:Q-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050765:Qa-SNARE Proteins / Q000235:genetics; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050767:Qc-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics; D033921:Vesicular Transport Proteins
chemical_list: D000071183:Autophagy-Related Proteins; D029742:Caenorhabditis elegans Proteins; C000592185:EPG5 protein, human; D051907:Lysosomal Membrane Proteins; D011506:Proteins; D050682:Q-SNARE Proteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; D034741:RNA, Small Interfering; C562341:SNAP-29 protein, C elegans; C432420:SNAP29 protein, human; C551267:STX17 protein, human; C112938:VAMP8 protein, human; D033921:Vesicular Transport Proteins; D049452:Green Fluorescent Proteins; D017351:N-Acetylglucosaminyltransferases; C063057:UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase; D000117:Acetylglucosamine