Cytosolic O-glycosylation is abundant in nerve terminals

Robert N. Cole, Gerald W. Hart

Research output: Contribution to journalArticlepeer-review

146 Scopus citations


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: β-N-acetylglucosamine linked to hydroxyls of serines or threonines (O-GlcNAc. 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-β-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-GIcNAc modified proteins: collapsin response mediator protein-2 (CRMP-2), ubiquitin carboxyl hydrolase-L1 (UCH-L1) and β-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.

Original languageEnglish (US)
Pages (from-to)1080-1089
Number of pages10
JournalJournal of Neurochemistry
Issue number5
StatePublished - 2001


  • Collapsin response mediator protein-2 (CRMP-2/DRP/TOAD-64/Ulip)
  • Gracile axonal dystrophy
  • Neurophosphoprotein 14
  • Parkinson's disease
  • Ubiquitin carboxyl hydrolase-L1 (UCH-L1/PGP9.5)
  • β-synuclein

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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