Cited by 364Glycosylation and Glycoproteins ResearchAlzheimer's disease research and treatmentsCarbohydrate Chemistry and Synthesis

The Microtubule-associated Protein Tau Is Extensively Modified with O-linked N-acetylglucosamine

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Arnold, C. Shane, Johnson, GailV.W., Cole, Robert N., Dong, Dennis L.-Y., Lee, Michael, Hart, Gerald W.·1996·Journal of Biological Chemistry

Abstract

Tau is a family of phosphoproteins that are important in modulating microtubule stability in neurons. In Alzheimer's disease tau is abnormally hyperphosphorylated, no longer binds microtubules, and self-assembles to form paired helical filaments that likely contribute to neuron death. Here we demonstrate that normal bovine tau is multiply modified by Ser(Thr)-O-linked N-acetylglucosamine, a dynamic and abundant post-translational modification that is often reciprocal to Ser(Thr)-phosphorylation. O-GlcNAcylation of tau was demonstrated by blotting with succinylated wheat germ agglutinin and by probing with bovine milk beta(1,4)galactosyltransferase. Structural analyses confirm the linkage and the saccharide structure. Tau splicing variants are multiply O-GlcNAcylated at similar sites, with an average stoichiometry of greater than 4 mol of O-linked N-acetylglucosamine/mol of tau. However, the number of sites occupied appears to be greater than 12, suggesting substoichiometric occupancy at any given site. A similar relationship between average stoichiometry and site-occupancy has also been described for the phosphorylation of tau. Site-specific or stoichiometric changes in O-GlcNAcylation may not only modulate tau function but may also play a role in the formation of paired helical filaments.

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Crossref · 10.1074/jbc.271.46.28741

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Authors
Arnold, C. S., Johnson, G. W., Cole, R. N., Dong, D. L.-Y., Lee, M., & Hart, G. W.
Affiliations
University of Alabama at Birmingham (US)
Corresponding author
Hart, Gerald W.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1996-11
Volume
271
Issue
46
Pages
28741-28744
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2066371153
Cited by
361
References
61
Citations by year
2026: 3 · 2025: 12 · 2024: 17 · 2023: 10 · 2022: 12 · 2021: 17 · 2020: 20 · 2019: 13 · 2018: 19 · 2017: 13 · 2016: 18 · 2015: 11 · 2014: 18 · 2013: 12 · 2012: 10
FWCI
2.15
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01ns027538-10)
  • National Cancer Institute (R01CA42486, R01CA042486)
  • National Institute of General Medical Sciences (T32GM008111, 5-T32-GM08111-10)
  • National Institute of Neurological Disorders and Stroke (R01 NS 27538)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glycosylation and Glycoproteins Research
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Chemistry › Organic Chemistry › Carbohydrate Chemistry and Synthesis
Keywords
tau protein, O-GlcNAcylation, N-acetylglucosamine, post-translational modification, paired helical filaments, Alzheimer's disease, microtubule binding, phosphorylation, site occupancy
MeSH terms
Acetylglucosamine, Amino Acid Sequence, Animals, Brain Chemistry, Cattle, Galactosyltransferases, Glycosylation, Molecular Sequence Data, Phosphorylation, tau Proteins

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