title: Microtubule destruction induces tau liberation and its subsequent phosphorylation.
abstract: 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.
authors.affiliation: Laboratory for Alzheimer's Disease, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN),Wako-shi, Saitama, Japan. tomiyasa@mail.doshisha.ac.jp
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Miyasaka
authors.forename: Sinji
authors.initials: S
authors.lastname: Sato
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Tatebayashi
authors.forename: Akihiko
authors.initials: A
authors.lastname: Takashima
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008870:Microtubules / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D016874:Neurofibrillary Tangles; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D016875:tau Proteins; D048031:JNK Mitogen-Activated Protein Kinases