Cytosolic O-glycosylation is abundant in nerve terminals

J Neurochem. 2001 Dec;79(5):1080-9. doi: 10.1046/j.1471-4159.2001.00655.x.


Phosphorylation plays a key role in regulating growth cone migration and protein trafficking in nerve terminals. Here we show that nerve terminal proteins contain another abundant post-translational modification: beta-N-acetylglucosamine linked to hydroxyls of serines or threonines (O-GlcNAc(1)). O-GlcNAc modifications are essential for embryogenesis and mounting evidence suggests that O-GlcNAc is a regulatory modification that affects many phosphorylated proteins. We show that the activity and expression of O-GlcNAc transferase (OGT) and N-acetyl-beta-D-glucosaminidase (O-GlcNAcase), the two enzymes regulating O-GlcNAc modifications, are present in nerve terminal structures (synaptosomes) and are particularily abundant in the cytosol of synaptosomes. Numerous synaptosome proteins are highly modified with O-GlcNAc. Although most of these proteins are present in low abundance, we identified by proteomic analysis three neuron-specific O-GlcNAc modified proteins: collapsin response mediator protein-2 (CRMP-2), ubiquitin carboxyl hydrolase-L1 (UCH-L1) and beta-synuclein. CRMP-2, which is involved in growth cone collapse, is a major O-GlcNAc modified protein in synaptosomes. All three proteins are implicated in regulatory cascades that mediate intracellular signaling or neurodegenerative diseases. We propose that O-GlcNAc modifications in the nerve terminal help regulate the functions of these and other synaptosome proteins, and that O-GlcNAc may play a role in neurodegenerative disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylglucosamine / metabolism*
  • Amino Acid Sequence
  • Animals
  • Blotting, Western
  • Brain Chemistry
  • Carbohydrate Metabolism
  • Cytosol / enzymology
  • Cytosol / metabolism*
  • Galactosyltransferases / metabolism
  • Glycosylation
  • Hydrolysis
  • In Vitro Techniques
  • Mass Spectrometry
  • Molecular Sequence Data
  • Nerve Endings / enzymology
  • Nerve Endings / metabolism*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / chemistry
  • Neurons / metabolism
  • Protein Processing, Post-Translational
  • Rats
  • Rats, Sprague-Dawley
  • Serine / analogs & derivatives*
  • Serine / metabolism*
  • Spectrometry, Fluorescence
  • Subcellular Fractions / metabolism
  • Synaptosomes / metabolism
  • Trypsin


  • Nerve Tissue Proteins
  • Serine
  • Galactosyltransferases
  • Trypsin
  • Acetylglucosamine