Global identification and characterization of both O-GlcNAcylation and phosphorylation at the murine synapse

Mol Cell Proteomics. 2012 Aug;11(8):215-29. doi: 10.1074/mcp.O112.018366. Epub 2012 May 29.

Abstract

O-linked N-acetylglucosamine (O-GlcNAc) is a dynamic, reversible monosaccharide modifier of serine and threonine residues on intracellular protein domains. Crosstalk between O-GlcNAcylation and phosphorylation has been hypothesized. Here, we identified over 1750 and 16,500 sites of O-GlcNAcylation and phosphorylation from murine synaptosomes, respectively. In total, 135 (7%) of all O-GlcNAcylation sites were also found to be sites of phosphorylation. Although many proteins were extensively phosphorylated and minimally O-GlcNAcylated, proteins found to be extensively O-GlcNAcylated were almost always phosphorylated to a similar or greater extent, indicating the O-GlcNAcylation system is specifically targeting a subset of the proteome that is also phosphorylated. Both PTMs usually occur on disordered regions of protein structure, within which, the location of O-GlcNAcylation and phosphorylation is virtually random with respect to each other, suggesting that negative crosstalk at the structural level is not a common phenomenon. As a class, protein kinases are found to be more extensively O-GlcNAcylated than proteins in general, indicating the potential for crosstalk of phosphorylation with O-GlcNAcylation via regulation of enzymatic activity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylglucosamine / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Brain / metabolism
  • Chromatography, Reverse-Phase
  • Glycosylation
  • Mass Spectrometry
  • Mice
  • Mice, Inbred C57BL
  • N-Acetylglucosaminyltransferases / genetics
  • Peptides / analysis*
  • Peptides / metabolism
  • Phosphorylation
  • Protein Processing, Post-Translational
  • Proteins / analysis
  • Proteins / metabolism
  • Proteomics / methods
  • Synapses / metabolism*
  • Synaptic Membranes / metabolism
  • Synaptosomes / metabolism*

Substances

  • Peptides
  • Proteins
  • N-Acetylglucosaminyltransferases
  • Acetylglucosamine