Journal
FEBS LETTERS
Volume 584, Issue 14, Pages 3227-3232Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.febslet.2010.06.014
Keywords
Tau; Microtubule; Phosphorylation; Stathmin; Neurofibrillary tangle; Alzheimer's disease
Funding
- JSPS KAKENHI
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Neurofibrillary tangle-bearing neurons, a pathological hallmark of Alzheimer's disease, are mostly devoid of normal microtubule (MT) structure and instead have paired helical filaments that are composed of abnormal hyperphosphorylated tau. However, a causal relationship between tau phosphorylation and MT disruption has not been clarified. To examine whether MT disruption induces tau phosphorylation, stathmin, an MT-disrupting protein, was co-expressed with tau in COS-7 cells. Stathmin expression induced apparent MT catastrophe and tau hyperphosphorylation at Thr-181, Ser-202, Thr-205, and Thr-231 sites. In contrast, c-Jun N-terminal kinase activation, or phosphatase inhibition, led to significant tau phosphorylation without affecting MT structure. These findings suggest that MT disruption induces subsequent tau phosphorylation. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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