Microtubule destruction induces tau liberation and its subsequent phosphorylation
Microtubule destruction induces tau liberation and its subsequent phosphorylation
复制标题
DOI：
10.1016/j.febslet.2010.06.014
复制
发表时间：
2010-07-16
期刊：
影响因子：
3.5
通讯作者：
Takashima, Akihiko
中科院分区：
文献类型：
--
作者：
Miyasaka, Tomohiro;Sato, Sinji;Takashima, Akihiko
神经原纤维缠结神经元是阿尔茨海默病的一个病理标志，它大多缺乏正常的微管(MT)结构，而是由异常的过度磷酸化tau组成的成对螺旋细丝。然而，tau磷酸化和MT中断之间的因果关系尚未阐明。为了研究MT干扰是否诱导tau的磷酸化，在COS-7细胞中共表达了一种MT干扰蛋白stathmin。Stathmin表达可诱导Thr-181、Ser-202、Thr-205和Thr-231位点明显的MT突变和tau过度磷酸化。相反，c-jun氨基末端的激活或磷酸酶抑制，导致显著的tau磷酸化，而不影响MT的结构。这些发现表明，MT的破坏导致随后的tau磷酸化。(C)2010年欧洲生化学会联合会。爱思唯尔出版，版权所有。
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.