RRC ID 45736
Author Guo B, Liang Q, Li L, Hu Z, Wu F, Zhang P, Ma Y, Zhao B, Kovács AL, Zhang Z, Feng D, Chen S, Zhang H.
Title O-GlcNAc-modification of SNAP-29 regulates autophagosome maturation.
Journal Nat Cell Biol
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.
Volume 16(12)
Pages 1215-26
Published 2014-12-1
DOI 10.1038/ncb3066
PII ncb3066
PMID 25419848
MeSH Acetylglucosamine / metabolism* Animals Autophagy / physiology* Autophagy-Related Proteins Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Endosomes / physiology* Green Fluorescent Proteins / genetics HeLa Cells Humans Lysosomal Membrane Proteins Lysosomes / physiology* Membrane Fusion* Mutation N-Acetylglucosaminyltransferases / genetics N-Acetylglucosaminyltransferases / metabolism* Phagosomes / physiology* Protein Binding Proteins / genetics Q-SNARE Proteins / genetics Q-SNARE Proteins / metabolism Qa-SNARE Proteins / genetics Qb-SNARE Proteins / genetics Qb-SNARE Proteins / metabolism* Qc-SNARE Proteins / genetics Qc-SNARE Proteins / metabolism* R-SNARE Proteins / genetics RNA Interference RNA, Small Interfering Signal Transduction / genetics Vesicular Transport Proteins
IF 20.042
Times Cited 116
C.elegans tm3425 tm1036 tm1046