Anesthesia-induced hyperphosphorylation detaches 3-repeat tau from microtubules without affecting their stability in vivo.
Anesthesia-induced hyperphosphorylation detaches 3-repeat tau from microtubules without affecting their stability in vivo.
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DOI：
10.1523/jneurosci.4101-08.2008
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发表时间：
2008-11-26
期刊：
影响因子：
--
通讯作者：
Duff KE
中科院分区：
文献类型：
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作者：
Planel E;Krishnamurthy P;Miyasaka T;Liu L;Herman M;Kumar A;Bretteville A;Figueroa HY;Yu WH;Whittington RA;Davies P;Takashima A;Nixon RA;Duff KE
在阿尔茨海默病中，tau蛋白被过度磷酸化，这被认为是使其与微管（MT）分离，诱导MT不稳定，并促进聚集。使用先前描述的体内模型，我们研究了过度磷酸化是否影响野生型和转基因小鼠中的tau蛋白功能。我们发现，麻醉诱导的低温后，无MT的tau蛋白被过度磷酸化，这损害了其结合MT和促进MT组装的能力。与游离tau相比，MT结合的tau对过度磷酸化更具抗性，并且tau在野生型小鼠中不与MT解离。然而，在转基因小鼠中，3-重复tau与MT分离。令人惊讶的是，tau从MT的解离并没有导致微管蛋白的明显解聚，并且没有轴突MT网络的崩溃或干扰。这些结果表明，在体内，与MT结合的tau亚群在广泛磷酸化tau的条件下不容易解离。在这些条件下保留在MT上的Tau足以维持MT网络完整性。
In Alzheimer’s disease, tau is hyperphosphorylated, which is thought to detach it from microtubules (MTs), induce MT destabilization, and promote aggregation. Using a previously described in vivo model, we investigated whether hyperphosphorylation impacts tau function in wild-type and transgenic mice. We found that following anesthesia-induced hypothermia, MT-free tau was hyperphosphorylated, which impaired its ability to bind MTs and promote MT assembly. MT-bound tau was more resistant to hyperphosphorylation compared to free tau and tau did not dissociate from MTs in wild-type mice. However, 3-repeat tau detached from MT in the transgenic mice. Surprisingly, dissociation of tau from MTs did not lead to overt depolymerization of tubulin, and there was no collapse, or disturbance of axonal MT networks. These results indicate that, in vivo, a sub-population of tau bound to MTs does not easily dissociate under conditions that extensively phosphorylate tau. Tau remaining on the MTs under these conditions is sufficient to maintain MT network integrity.