The DOI matches its Crossref record; 61 of the 61 references it cites were found in a registry or an index.
The Microtubule-associated Protein Tau Is Extensively Modified with O-linked N-acetylglucosamine
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Both N- and O-linked glycosylation have been identified in tau [182, 183].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [183]
Citations
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 316,394
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
A68: a Major Subunit of Paired Helical Filaments and Derivatized Forms of Normal Tau
Lee, V. M.-Y., Balin, B. J., Otvos, L., & Trojanowski, J. Q. (1991) · Science · doi:10.1126/science.1899488 · Cited by 1,418
Rosenfeld, J., Capdevielle, J., Guillemot, J. C., & Ferrara, P. (1992) · Analytical Biochemistry · doi:10.1016/0003-2697(92)90061-b · Cited by 1,239
Torres, C., & Hart, G. W. (1984) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)43295-9 · Cited by 1,132
Self-citationDeglycosylation of asparagine-linked glycans by peptide:N-glycosidase F
Tarentino, A. L., Gomez, C. M., & Plummer, T. H. (1985) · Biochemistry · doi:10.1021/bi00338a028 · Cited by 1,130
Goedert, M., Spillantini, M. G., Potier, M. C., Ulrich, J., & Crowther, R. A. (1989) · The EMBO Journal · doi:10.1002/j.1460-2075.1989.tb03390.x · Cited by 1,037
Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau.
Drechsel, D. N., Hyman, A. A., Cobb, M. H., & Kirschner, M. W. (1992) · Molecular Biology of the Cell · doi:10.1091/mbc.3.10.1141 · Cited by 1,011
Physical and chemical properties of purified tau factor and the role of tau in microtubule assembly
Cleveland, D. W., Hwo, S. Y., & Kirschner, M. W. (1977) · Journal of Molecular Biology · doi:10.1016/0022-2836(77)90214-5 · Cited by 881
Ubiquitin Is a Component of Paired Helical Filaments in Alzheimer's Disease
Mori, H., Kondo, J., & Ihara, Y. (1987) · Science · doi:10.1126/science.3029875 · Cited by 843
Tau protein function in living cells.
Drubin, D. G., & Kirschner, M. W. (1986) · The Journal of Cell Biology · doi:10.1083/jcb.103.6.2739 · Cited by 766
The Primary Structure and Heterogeneity of Tau Protein from Mouse Brain
Lee, G. S., Cowan, N. J., & Kirschner, M. W. (1988) · Science · doi:10.1126/science.3122323 · Cited by 680
Brandt, R., Léger, J. G., & Lee, G. S. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.131.5.1327 · Cited by 663
Proline-directed and non-proline-directed phosphorylation of PHF-tau
Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Yoshida, H., Titani, K., & Ihara, Y. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.2.823 · Cited by 557
Himmler, A., Drechsel, D. N., Kirschner, M. W., & Martin, D. W. (1989) · Molecular and Cellular Biology · doi:10.1128/mcb.9.4.1381-1388.1989 · Cited by 555
Hardy, M. R., Townsend, R. R., & Lee, Y. C. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90089-9 · Cited by 538
Phosphorylated Tau Protein Is Integrated into Paired Helical Filaments in Alzheimer's Disease1
Ihara, Y., Nukina, N., Miura, R., & OGAWARA, M. (1986) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a135662 · Cited by 527
Dong, D. L., & Hart, G. W. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32170-1 · Cited by 508
Self-citationDYNAMIC O-LINKED GLYCOSYLATION OF NUCLEAR AND CYTOSKELETAL PROTEINS
Hart, G. W. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.315 · Cited by 503
Self-citationSugar‐Lectin Interactions: How Does Wheat‐Germ Agglutinin Bind Sialoglycoconjugates?
Monsigny, M. L. P., Roche, A., Sené, C., Maget‐Dana, R., & DELMOTTE, F. (1980) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1980.tb04410.x · Cited by 465
Chou, T.-Y., Hart, G. W., & Dang, C. V. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.32.18961 · Cited by 453
Self-citationMeek, J. L. (1980) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.77.3.1632 · Cited by 445
Haltiwanger, R. S., Blomberg, M. A., & Hart, G. W. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50380-5 · Cited by 444
Self-citationNuclear pore complex glycoproteins contain cytoplasmically disposed O-linked N-acetylglucosamine.
Holt, G. D., Snow, C. M., Senior, A., Haltiwanger, R. S., Gerace, L., & Hart, G. W. (1987) · The Journal of Cell Biology · doi:10.1083/jcb.104.5.1157 · Cited by 444
Self-citationProtein sequence and mass spectrometric analyses of tau in the Alzheimer's disease brain
Hasegawa, M., Morishima-Kawashima, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41890-x · Cited by 430
RNA polymerase II is a glycoprotein. Modification of the COOH-terminal domain by O-GlcNAc
Kelly, W. G., Dahmus, M. E., & Hart, G. W. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)82216-5 · Cited by 407
Self-citationMicrotubule-associated Protein/Microtubule Affinity-regulating Kinase (p110mark)
Meyer, H. E., Mandelkow, E.-M., Drewes, G., Trinczek, B., Illenberger, S., Biernat, J., Schmitt-Ulms, G., & Mandelkow, E. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7679 · Cited by 388
GLYCOSYLATION IN THE NUCLEUS AND CYTOPLASM
Hart, G. W., Haltiwanger, R. S., Holt, G. D., & Kelly, W. G. (1989) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.58.070189.004205 · Cited by 386
Self-citationWang, J.-Z., Grundke-Iqbal, I., & Iqbal, K. (1996) · Nature Medicine · doi:10.1038/nm0896-871 · Cited by 360
Analysis of microtubule-associated protein tau glycation in paired helical filaments.
Ledesma, M. D., Bonay, P., Colaço, C., & Avila, J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)31849-5 · Cited by 333
Ubiquitin is conjugated with amino-terminally processed tau in paired helical filaments
Morishima-Kawashima, M., Hasegawa, M., Takio, K., Suzuki, M., Titani, K., & Ihara, Y. (1993) · Neuron · doi:10.1016/0896-6273(93)90063-w · Cited by 332
Protein determination using bicinchoninic acid in the presence of sulfhydryl reagents
Hill, H. D., & Straka, J. G. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90109-1 · Cited by 305
Microheterogeneity and paucidispersity of glycoproteins
Huang, C., Mayer, H. E., & Montgomery, R. (1970) · Carbohydrate Research · doi:10.1016/s0008-6215(00)84902-2 · Cited by 274
Identification of nuclear tau isoforms in human neuroblastoma cells.
Loomis, P. A., Howard, T. H., Castleberry, R. P., & Binder, L. I. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.21.8422 · Cited by 251
Lymphocyte activation induces rapid changes in nuclear and cytoplasmic glycoproteins.
Kearse, K. P., & Hart, G. W. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.5.1701 · Cited by 232
Self-citationCharacterization and dynamics of O-linked glycosylation of human cytokeratin 8 and 18.
Chou, C.-F., Smith, A. J., & Omary, M. B. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)50611-1 · Cited by 212
Dong, D. L., Xu, Z. S., Chevrier, M. R., Cotter, R. J., Cleveland, D. W., & Hart, G. W. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85471-6 · Cited by 204
Self-citationShaw, P., Freeman, J., Bovey, R., & Iggo, R. D. (1996) · PubMed · Cited by 202
Phosphorylation by cAMP-dependent protein kinase inhibits the degradation of tau by calpain.
Litersky, J. M., & Johnson, G. V. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45982-0 · Cited by 201
Self-citationGlycosylation of nuclear and cytoplasmic proteins is ubiquitous and dynamic
Haltiwanger, R. S., Kelly, W. G., Roquemore, E. P., Blomberg, M. A., Dong, L.-Y. D., Kreppel, L. K., Chou, T., & Hart, G. W. (1992) · Biochemical Society Transactions · doi:10.1042/bst0200264 · Cited by 186
Self-citationBancher, C., Grundke, I., Iqbal, K., Fried, V. A., Smith, H. T., & Wisniewski, H. M. (1991) · Brain Research · doi:10.1016/0006-8993(91)90681-k · Cited by 185
Greis, K. D., Hayes, B. K., Comer, F. I., KIRK, M. C., Barnes, S., Lowary, T. L., & Hart, G. W. (1996) · Analytical Biochemistry · doi:10.1006/abio.1996.0047 · Cited by 175
Self-citationDynamic O-GlcNAcylation of the Small Heat Shock Protein αB-Crystallin
Roquemore, E. P., Chevrier, M. R., Cotter, R. J., & Hart, G. W. (1996) · Biochemistry · doi:10.1021/bi951918j · Cited by 171
Self-citationJohnson, G. V. W., Jope, R. S., & Binder, L. I. (1989) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(89)91150-9 · Cited by 161
Self-citationβ‐Amyloid precursor protein is modified with O‐linked N‐acetylglucosamine
Griffith, L. S., Mathes, M., & Schmitz, B. (1995) · Journal of Neuroscience Research · doi:10.1002/jnr.490410214 · Cited by 154
[26] Detection of O-Linked N-acetylglucosamine (O-GlcNAc) on cytoplasmic and nuclear proteins
Roquemore, E. P., Chou, T., & Hart, G. W. (1994) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(94)30028-3 · Cited by 136
Self-citationDatta, B., Ray, M. K., Chakrabarti, D., Wylie, D. E., & Gupta, N. K. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47108-1 · Cited by 133
O-Linked N-Acetylglucosamine Is Upregulated in Alzheimer Brains
Griffith, L. S., & Schmitz, B. (1995) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1995.2149 · Cited by 112
Vertebrate lens alpha-crystallins are modified by O-linked N-acetylglucosamine.
Roquemore, E. P., Dell, A., Morris, H. R., Panico, M., Reason, A. J., Savoy, L.-A., Wistow, G. J., Zigler, J. S., Earles, B. J., & Hart, G. W. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48530-4 · Cited by 105
Self-citationA manual sequencing method for identification of phosphorylated amino acids in phosphopeptides
Sullivan, S., & Wong, T. W. (1991) · Analytical Biochemistry · doi:10.1016/0003-2697(91)90356-x · Cited by 86
Datta, B., Chakrabarti, D., Roy, A. L., & Gupta, N. K. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.10.3324 · Cited by 83
Differential Binding of Apolipoprotein E Isoforms to Tau and Other Cytoskeletal Proteins
Fleming, L. M., Weisgraber, K. H., Strittmatter, W. J., Troncoso, J. C., & Johnson, G. V. W. (1996) · Experimental Neurology · doi:10.1006/exnr.1996.0064 · Cited by 82
Self-citationHigh Molecular Weight Microtubule-associated Proteins Contain O-Linked N-Acetylglucosamine
Ding, M., & Vandré, D. D. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.21.12555 · Cited by 64
Specific Isolation of O-Linked N-Acetylglucosamine Glycopeptides from Complex Mixtures
Hayes, B. K., Greis, K. D., & Hart, G. W. (1995) · Analytical Biochemistry · doi:10.1006/abio.1995.1322 · Cited by 53
Self-citationSynapsins Contain O‐Linked N‐Acetylglucosamine
Liithi, T., Haltiwanger, R. S., Greengard, P., & Bähler, M. (1991) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1991.tb02043.x · Cited by 43
Tau 2: A Probe for a Ser Conformation in the Amino Terminus of τ
Watanabe, N., Takio, K., Hasegawa, M., Aral, T., Titani, K., & Ihara, Y. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09349.x · Cited by 42
Glutamate Synthase from Bacillus subtilis PCI 2191
Matsuoka, K., & Kimura, K. (1986) · The Journal of Biochemistry · doi:10.1093/oxfordjournals.jbchem.a135573 · Cited by 29
Hayes, B. K., & Varki, A. P. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85402-9 · Cited by 25
DNA Replication and the Cell Cycle
Fanning, E., Knippers, R., & Winnacker, E. (1993) · Springer eBooks · doi:10.1007/978-3-642-77040-1 · Cited by 24
Specific Processing of Native and Phosphorylated τ Protein by Proteases
Wang, X., An, S., & Wu, J. M. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.0278 · Cited by 16
Ubiquitous and temporal glycosylation of nuclear and cytoplasmic proteins
Hart, G. W., Greis, K. D., Dong, L.-Y. D., Blomberg, M. A., Chou, T.-Y., Jiang, M., Roquemore, E. P., Snow, D. M., Kreppel, L. K., Cole, R. C., et al. (1995) · Pure and Applied Chemistry · doi:10.1351/pac199567101637 · Cited by 16
Self-citation
Flagged first, then by citations
Research works printed but not linked: 3
- Himmler, 1989, Mol. Cell. Biol., 9, 1381
- Shaw, 1996, Oncogene, 12, 921
- Schaffner, 1973, Anal. Biochem., 197, 65
Cited by
Sorted by citations
Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders
Ballatore, C., Lee, V. M.-Y., & Trojanowski, J. Q. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2194 · Cited by 2,174
Buée, L., Bussière, T., Buée‐Scherrer, V., Delacourte, A., & Hof, P. R. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00019-9 · Cited by 2,142
Protein Analysis by Shotgun/Bottom-up Proteomics
Zhang, Y., Fonslow, B. R., Shan, B., Baek, M.-C., & Yates, J. R. (2013) · Chemical Reviews · doi:10.1021/cr3003533 · Cited by 1,491
Hart, G. W., Slawson, C., Ramirez-Correa, G., & Lagerlof, O. (2011) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060608-102511 · Cited by 1,317
Self-citationTau pathology and neurodegeneration
Spillantini, M. G., & Goedert, M. (2013) · The Lancet Neurology · doi:10.1016/s1474-4422(13)70090-5 · Cited by 1,133
Metadata
- 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
- hybrid
- doi.org
- Licence
- 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
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
