Premium
Microtubule destruction induces tau liberation and its subsequent phosphorylation
Author(s) -
Miyasaka Tomohiro,
Sato Sinji,
Tatebayashi Yoshitaka,
Takashima Akihiko
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.06.014
Subject(s) - phosphorylation , stathmin , hyperphosphorylation , microtubule , phosphatase , chemistry , microbiology and biotechnology , cyclin dependent kinase 5 , dephosphorylation , tau protein , kinase , biology , protein kinase a , alzheimer's disease , medicine , mitogen activated protein kinase kinase , disease
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.