Abstract
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 language | English (US) |
---|---|
Pages (from-to) | 1080-1089 |
Number of pages | 10 |
Journal | Journal of Neurochemistry |
Volume | 79 |
Issue number | 5 |
DOIs | |
State | Published - 2001 |
Keywords
- 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