The microtubule-associated protein tau is extensively modified with O- linked N-acetylglucosamine

C. Shane Arnold, Gail V.W. Johnson, Robert N. Cole, Dennis L.Y. Dong, Michael Lee, Gerald W. Hart

Research output: Contribution to journalArticle

239 Citations (Scopus)

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-acetyl-glucosamine, 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 β(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 tool 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.

Original languageEnglish (US)
Pages (from-to)28741-28744
Number of pages4
JournalJournal of Biological Chemistry
Volume271
Issue number46
DOIs
StatePublished - Nov 26 1996

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Phosphorylation
Microtubule-Associated Proteins
Acetylglucosamine
Microtubules
Stoichiometry
Neurons
Galactosyltransferases
Phosphoproteins
Glucosamine
Post Translational Protein Processing
Alzheimer Disease
Milk
succinylated wheat germ agglutinin

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The microtubule-associated protein tau is extensively modified with O- linked N-acetylglucosamine. / Shane Arnold, C.; Johnson, Gail V.W.; Cole, Robert N.; Dong, Dennis L.Y.; Lee, Michael; Hart, Gerald W.

In: Journal of Biological Chemistry, Vol. 271, No. 46, 26.11.1996, p. 28741-28744.

Research output: Contribution to journalArticle

Shane Arnold, C. ; Johnson, Gail V.W. ; Cole, Robert N. ; Dong, Dennis L.Y. ; Lee, Michael ; Hart, Gerald W. / The microtubule-associated protein tau is extensively modified with O- linked N-acetylglucosamine. In: Journal of Biological Chemistry. 1996 ; Vol. 271, No. 46. pp. 28741-28744.
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