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.
Publication types
-
Research Support, N.I.H., Extramural
-
Research Support, Non-U.S. Gov't
MeSH terms
-
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
Substances
-
Autophagy-Related Proteins
-
Caenorhabditis elegans Proteins
-
EPG5 protein, human
-
Lysosomal Membrane Proteins
-
Proteins
-
Q-SNARE Proteins
-
Qa-SNARE Proteins
-
Qb-SNARE Proteins
-
Qc-SNARE Proteins
-
R-SNARE Proteins
-
RNA, Small Interfering
-
SNAP-29 protein, C elegans
-
SNAP29 protein, human
-
STX17 protein, human
-
VAMP8 protein, human
-
Vesicular Transport Proteins
-
Green Fluorescent Proteins
-
N-Acetylglucosaminyltransferases
-
UDP-N-acetylglucosamine-peptide beta-N-acetylglucosaminyltransferase
-
Acetylglucosamine