Gem GTPase and Tau - Morphological changes induced by Gem GTPase in Cho cells are antagonized by tau
Gem GTPase and Tau - Morphological changes induced by Gem GTPase in Cho cells are antagonized by tau
复制标题
DOI：
10.1074/jbc.m401634200
复制
发表时间：
2004-06-25
影响因子：
4.8
通讯作者：
Ihara, Y
中科院分区：
文献类型：
--
作者：
Oyama, F;Kotliarova, S;Ihara, Y
一系列的观察表明，tau蛋白，一个主要的微管相关蛋白，参与神经细胞的形态发生和轴突的维护。Tau也是在受阿尔茨海默病影响的大脑中发现的成对螺旋丝的主要成分。为了探索tau在体内尚未确定的作用，从tau缺陷小鼠大脑中分析了类似于11，000个mRNA，并与相同年龄的对照大脑进行了比较。Gem GT3是ras超家族的一种小GTP结合蛋白，其表达在8周龄tau缺陷小鼠的脑中显著增加。由于Gem GT3是细胞骨架组织的Rho-Rho激酶途径的负调节剂，因此该蛋白在不表达tau的中国仓鼠卵巢细胞中瞬时过表达。Gem GT3的过表达诱导中国仓鼠卵巢细胞显著伸长，同时表达tau消除了这种效应，尽管tau不直接与Gem GT3结合。tau蛋白的这种抗延伸活性归因于其微管结合结构域，微管相关蛋白2和4的同源结构域表现出类似的拮抗活性。两者合计，目前的结果表明，Gem GTP酶的水平和它的细胞伸长活性的调节tau蛋白，并表明，tau蛋白可能参与Gem GTP酶介导的信号转导途径。
A series of observations have indicated that tau, one of the major microtubule-associated proteins, is involved in neuronal cell morphogenesis and axonal maintenance. Tau is also the major component of paired helical filaments found in brains affected by Alzheimer's disease. To explore an as yet unidentified role of tau in vivo, similar to 11,000 mRNAs were profiled from tau-deficient mouse brains and compared with those from control brains at the same ages. The expression of Gem GTPase, a small GTP-binding protein of the ras superfamily, was significantly increased in the brains of tau-deficient mice at 8 weeks of age. Because Gem GTPase is a negative regulator of the Rho-Rho kinase pathway for cytoskeletal organization, this protein was transiently overexpressed in Chinese hamster ovary cells that do not express tau. Overexpression of Gem GTPase induced a marked elongation of Chinese hamster ovary cells, and simultaneous expression of tau eliminated this effect, although tau did not bind directly to Gem GTPase. This anti-elongation activity of tau was attributed to its microtubule-binding domain, and homologous domains of microtubule-associated proteins 2 and 4 exhibited similar antagonistic activities. Taken together, the present results indicate that the level of Gem GTPase and its cell elongation activity are modulated by tau and suggest that tau may be involved in a Gem GTPase-mediated signal transduction pathway.