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Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice

Kurt Spittaels, Chris Van den Haute, Jo Van Dorpe UGent, Hugo Geerts, Marc Mercken, Koen Bruynseels, Reena Lasrado, Kris Vandezande, Isabelle Laenen, Tim Boon, et al. (2000) JOURNAL OF BIOLOGICAL CHEMISTRY. 275(52). p.41340-41349
abstract
Protein tau filaments in brain of patients suffering from Alzheimer's disease, frontotemporal dementia, and other tauopathies consist of protein tau that is hyperphosphorylated.,The responsible kinases operating in vivo in neurons still need to be identified. Here we demonstrate that glycogen synthase kinase-3 beta (GSK-3 beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3 beta and GSK-3 beta x human tau40 transgenic mice; Phosphorylated protein tau migrates slower during electrophoretic separation and is revealed by phosphorylation-dependent anti-tau antibodies in Western blot analysis. In addition, its capacity to bind to re-assembled paclitaxel (Taxol(R))-stabilized microtubules is reduced, compared with protein tau isolated from mice not overexpressing GSK-3 beta. Co-expression of GSK-3 beta reduces the number of axonal dilations and alleviates the motoric impairment that was typical for single htau40 transgenic animals (Spittaels, K., Van den Haute, C., Van Dorpe, J., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R., Van Lommel, A., Loos, R., and Van Leuven, F. (1999) Am. J. Pathol. 155, 2153-2165). Although more hyperphosphorylated protein tau is available, neither an increase in insoluble protein tau aggregates nor the presence of paired helical filaments or tangles was observed. These findings could have therapeutic implications in the field of neurodegeneration, as discussed.
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author
organization
alternative title
Glycogen synthase kinase-3 beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice
year
type
journalArticle (original)
publication status
published
subject
keyword
AMYLOID PRECURSOR PROTEIN, PAIRED HELICAL FILAMENTS, DISEASE-LIKE PHOSPHORYLATION, ALZHEIMER-LIKE STATE, HUMAN BRAIN TAU, INTACT-CELLS, KINASE-I, MICROTUBULE-BINDING, NEUROFIBRILLARY TANGLES, MONOCLONAL-ANTIBODIES
journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
J. Biol. Chem.
volume
275
issue
52
pages
41340 - 41349
Web of Science type
Article
Web of Science id
000166114600090
ISSN
0021-9258
DOI
10.1074/jbc.M006219200
language
English
UGent publication?
no
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
5940728
handle
http://hdl.handle.net/1854/LU-5940728
date created
2015-04-22 10:32:33
date last changed
2016-12-19 15:47:28
@article{5940728,
  abstract     = {Protein tau filaments in brain of patients suffering from Alzheimer's disease, frontotemporal dementia, and other tauopathies consist of protein tau that is hyperphosphorylated.,The responsible kinases operating in vivo in neurons still need to be identified. Here we demonstrate that glycogen synthase kinase-3 beta (GSK-3 beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3 beta and GSK-3 beta x human tau40 transgenic mice; Phosphorylated protein tau migrates slower during electrophoretic separation and is revealed by phosphorylation-dependent anti-tau antibodies in Western blot analysis. In addition, its capacity to bind to re-assembled paclitaxel (Taxol(R))-stabilized microtubules is reduced, compared with protein tau isolated from mice not overexpressing GSK-3 beta. Co-expression of GSK-3 beta reduces the number of axonal dilations and alleviates the motoric impairment that was typical for single htau40 transgenic animals (Spittaels, K., Van den Haute, C., Van Dorpe, J., Bruynseels, K., Vandezande, K., Laenen, I., Geerts, H., Mercken, M., Sciot, R., Van Lommel, A., Loos, R., and Van Leuven, F. (1999) Am. J. Pathol. 155, 2153-2165). Although more hyperphosphorylated protein tau is available, neither an increase in insoluble protein tau aggregates nor the presence of paired helical filaments or tangles was observed. These findings could have therapeutic implications in the field of neurodegeneration, as discussed.},
  author       = {Spittaels, Kurt and Van den Haute, Chris and Van Dorpe, Jo and Geerts, Hugo and Mercken, Marc and Bruynseels, Koen and Lasrado, Reena and Vandezande, Kris and Laenen, Isabelle and Boon, Tim and Van Lint, Jo and Vandenheede, Jacky and Moechars, Dieter and Loos, Ruth and Van Leuven, Fred},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keyword      = {AMYLOID PRECURSOR PROTEIN,PAIRED HELICAL FILAMENTS,DISEASE-LIKE PHOSPHORYLATION,ALZHEIMER-LIKE STATE,HUMAN BRAIN TAU,INTACT-CELLS,KINASE-I,MICROTUBULE-BINDING,NEUROFIBRILLARY TANGLES,MONOCLONAL-ANTIBODIES},
  language     = {eng},
  number       = {52},
  pages        = {41340--41349},
  title        = {Glycogen synthase kinase-3\ensuremath{\beta} phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice},
  url          = {http://dx.doi.org/10.1074/jbc.M006219200},
  volume       = {275},
  year         = {2000},
}

Chicago
Spittaels, Kurt, Chris Van den Haute, Jo Van Dorpe, Hugo Geerts, Marc Mercken, Koen Bruynseels, Reena Lasrado, et al. 2000. “Glycogen Synthase Kinase-3β Phosphorylates Protein Tau and Rescues the Axonopathy in the Central Nervous System of Human Four-repeat Tau Transgenic Mice.” Journal of Biological Chemistry 275 (52): 41340–41349.
APA
Spittaels, Kurt, Van den Haute, C., Van Dorpe, J., Geerts, H., Mercken, M., Bruynseels, K., Lasrado, R., et al. (2000). Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. JOURNAL OF BIOLOGICAL CHEMISTRY, 275(52), 41340–41349.
Vancouver
1.
Spittaels K, Van den Haute C, Van Dorpe J, Geerts H, Mercken M, Bruynseels K, et al. Glycogen synthase kinase-3β phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. JOURNAL OF BIOLOGICAL CHEMISTRY. 2000;275(52):41340–9.
MLA
Spittaels, Kurt, Chris Van den Haute, Jo Van Dorpe, et al. “Glycogen Synthase Kinase-3β Phosphorylates Protein Tau and Rescues the Axonopathy in the Central Nervous System of Human Four-repeat Tau Transgenic Mice.” JOURNAL OF BIOLOGICAL CHEMISTRY 275.52 (2000): 41340–41349. Print.