Furiya Y, Sahara N, Mori H
Department of Molecular Biology, Tokyo Institute of Psychiatry, Japan.
Neurosci Lett. 1993 Jun 25;156(1-2):67-9. doi: 10.1016/0304-3940(93)90441-m.
Tau proteins are one of the microtubule-associated proteins (MAPs) and show promoting activity on microtubule assembly. Tau proves to be the major constituent of Alzheimer's paired helical filaments, in which tau is found to be different from normal tau in that it is abnormally phosphorylated. To examine the effect of the abnormal phosphorylation on microtubule assembly, we obtained abnormally phosphorylated tau that was made in vitro by hyperphosphorylation with ATP or with ATP and okadaic acid, a drug inhibiting phosphatase, mainly 1 and 2A. We confirmed the biochemical properties of abnormally phosphorylated tau based on its retarded gel mobility and immunoreactivity to anti-PHF. We found that abnormally phosphorylated tau was able to promote the polymerization of microtubules but showed less activity as compared with normally phosphorylated tau. This effect of ATP on abnormal phosphorylation of tau was enhanced when okadaic acid was added in the phosphorylation reaction mixture during microtubule assembly. It is of significance that phosphatase activity as well as kinase activity are involved in the formation of abnormal tau. The present evidence suggests the simultaneous occurrence of microtubule disassembly and the pathogenesis of paired helical filaments following the abnormal phosphorylation of tau.
Tau蛋白是微管相关蛋白（MAPs）之一，对微管组装具有促进活性。Tau蛋白被证明是阿尔茨海默病成对螺旋丝的主要成分，其中发现Tau蛋白与正常Tau蛋白不同，因为它被异常磷酸化。为了研究异常磷酸化对微管组装的影响，我们获得了通过用ATP或ATP与冈田酸（一种主要抑制磷酸酶1和2A的药物）进行过度磷酸化而在体外制备的异常磷酸化的Tau蛋白。我们基于其在凝胶中的迁移率延迟和对抗PHF的免疫反应性证实了异常磷酸化Tau蛋白的生化特性。我们发现异常磷酸化的Tau蛋白能够促进微管的聚合，但与正常磷酸化的Tau蛋白相比活性较低。当在微管组装过程中将冈田酸添加到磷酸化反应混合物中时，ATP对Tau蛋白异常磷酸化的这种作用会增强。磷酸酶活性以及激酶活性参与异常Tau蛋白的形成具有重要意义。目前的证据表明，在Tau蛋白异常磷酸化之后，微管解聚和成对螺旋丝的发病机制会同时发生。
