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

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Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. / Spittaels, K; Van den Haute, C; Van Dorpe, J; Geerts, H; Mercken, M; Bruynseels, K; Lasrado, R; Vandezande, K; Laenen, I; Boon, T; Van Lint, J; Vandenheede, J; Moechars, D; Loos, R; Van Leuven, F.

In: The Journal of Biological Chemistry, Vol. 275, No. 52, 29.12.2000, p. 41340-9.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Spittaels, K, Van den Haute, C, Van Dorpe, J, Geerts, H, Mercken, M, Bruynseels, K, Lasrado, R, Vandezande, K, Laenen, I, Boon, T, Van Lint, J, Vandenheede, J, Moechars, D, Loos, R & Van Leuven, F 2000, 'Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice', The Journal of Biological Chemistry, vol. 275, no. 52, pp. 41340-9. https://doi.org/10.1074/jbc.M006219200

APA

Spittaels, K., Van den Haute, C., Van Dorpe, J., Geerts, H., Mercken, M., Bruynseels, K., Lasrado, R., Vandezande, K., Laenen, I., Boon, T., Van Lint, J., Vandenheede, J., Moechars, D., Loos, R., & Van Leuven, F. (2000). Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. The Journal of Biological Chemistry, 275(52), 41340-9. https://doi.org/10.1074/jbc.M006219200

Vancouver

Spittaels K, Van den Haute C, Van Dorpe J, Geerts H, Mercken M, Bruynseels K et al. Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. The Journal of Biological Chemistry. 2000 Dec 29;275(52):41340-9. https://doi.org/10.1074/jbc.M006219200

Author

Spittaels, K ; Van den Haute, C ; Van Dorpe, J ; Geerts, H ; Mercken, M ; Bruynseels, K ; Lasrado, R ; Vandezande, K ; Laenen, I ; Boon, T ; Van Lint, J ; Vandenheede, J ; Moechars, D ; Loos, R ; Van Leuven, F. / Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice. In: The Journal of Biological Chemistry. 2000 ; Vol. 275, No. 52. pp. 41340-9.

Bibtex

@article{c28595cea5054e8d9efd5812226cb7d1,
title = "Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice",
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-3beta (GSK-3beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3beta and GSK-3beta 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-3beta. Co-expression of GSK-3beta 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.",
keywords = "Alzheimer Disease/etiology, Animals, Axons/pathology, Brain/metabolism, Calcium-Calmodulin-Dependent Protein Kinases/physiology, Glycogen Synthase Kinases, Humans, Mice, Mice, Transgenic, Motor Activity, Phosphorylation, Solubility, Spinal Cord/metabolism, tau Proteins/chemistry",
author = "K Spittaels and {Van den Haute}, C and {Van Dorpe}, J and H Geerts and M Mercken and K Bruynseels and R Lasrado and K Vandezande and I Laenen and T Boon and {Van Lint}, J and J Vandenheede and D Moechars and R Loos and {Van Leuven}, F",
year = "2000",
month = dec,
day = "29",
doi = "10.1074/jbc.M006219200",
language = "English",
volume = "275",
pages = "41340--9",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology, Inc.",
number = "52",

}

RIS

TY - JOUR

T1 - Glycogen synthase kinase-3beta phosphorylates protein tau and rescues the axonopathy in the central nervous system of human four-repeat tau transgenic mice

AU - Spittaels, K

AU - Van den Haute, C

AU - Van Dorpe, J

AU - Geerts, H

AU - Mercken, M

AU - Bruynseels, K

AU - Lasrado, R

AU - Vandezande, K

AU - Laenen, I

AU - Boon, T

AU - Van Lint, J

AU - Vandenheede, J

AU - Moechars, D

AU - Loos, R

AU - Van Leuven, F

PY - 2000/12/29

Y1 - 2000/12/29

N2 - 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-3beta (GSK-3beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3beta and GSK-3beta 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-3beta. Co-expression of GSK-3beta 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.

AB - 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-3beta (GSK-3beta) is an effective kinase for protein tau in cerebral neurons in vivo in adult GSK-3beta and GSK-3beta 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-3beta. Co-expression of GSK-3beta 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.

KW - Alzheimer Disease/etiology

KW - Animals

KW - Axons/pathology

KW - Brain/metabolism

KW - Calcium-Calmodulin-Dependent Protein Kinases/physiology

KW - Glycogen Synthase Kinases

KW - Humans

KW - Mice

KW - Mice, Transgenic

KW - Motor Activity

KW - Phosphorylation

KW - Solubility

KW - Spinal Cord/metabolism

KW - tau Proteins/chemistry

U2 - 10.1074/jbc.M006219200

DO - 10.1074/jbc.M006219200

M3 - Journal article

C2 - 11007782

VL - 275

SP - 41340

EP - 41349

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 52

ER -

ID: 258040040