Tau Phosphorylation Sites Work in Concert to Promote Neurotoxicity In Vivo
- 1 December 2007
- journal article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 18 (12), 5060-5068
- https://doi.org/10.1091/mbc.e07-04-0327
Abstract
Tau is a microtubule binding protein implicated in a number of human neurodegenerative disorders, including Alzheimer's disease. Phosphorylation of serine-proline/threonine-proline sites, targeted by proline-directed kinases, coincides temporally with neurodegeneration in the human diseases. Recently, we demonstrated that this unique group of serines and threonines has a critical role in controlling tau toxicity in a Drosophila model of tauopathy. Here, we use a combination of genetic and biochemical approaches to examine these sites individually and to determine which of them is primarily responsible for controlling tau neurotoxicity. Despite the importance placed on individual phosphoepitopes and their contributions to disease pathogenesis, our results indicate that no single phosphorylation residue plays a dominant role in controlling tau toxicity. These findings suggest that serine-proline/threonine-proline sites cooperate to mediate neurodegeneration in vivo.Keywords
This publication has 46 references indexed in Scilit:
- S/P and T/P phosphorylation is critical for tau neurotoxicity in DrosophilaJournal of Neuroscience Research, 2007
- Oxidative stress mediates tau-induced neurodegeneration in DrosophilaJCI Insight, 2007
- Cell type‐specific processing of human Tau proteins in DrosophilaFEBS Letters, 2006
- Post-translational modifications of tau protein in Alzheimer’s diseaseJournal of Neural Transmission, 2004
- Up-Regulation of Phosphorylated/Activated p70 S6 Kinase and Its Relationship to Neurofibrillary Pathology in Alzheimer's DiseaseThe American Journal of Pathology, 2003
- Sequential phosphorylation of Tau by glycogen synthase kinase‐3β and protein kinase A at Thr212 and Ser214 generates the Alzheimer‐specific epitope of antibody AT100 and requires a paired‐helical‐filament‐like conformationEuropean Journal of Biochemistry, 1998
- Neurodegenerative disorders with extensive tau pathology: A comparative study and reviewAnnals of Neurology, 1996
- Monoclonal antibody AT8 recognises tau protein phosphorylated at both serine 202 and threonine 205Neuroscience Letters, 1995
- Rapid Alzheimer‐like phosphorylation of tau by the synergistic actions of non‐proline‐dependent protein kinases and GSK‐3FEBS Letters, 1995
- Abnormal tau species are produced during Alzheimer's disease neurodegenerating processFEBS Letters, 1989