Phosphorylation of tau by glycogen synthase kinase 3β in intact mammalian cells influences the stability of microtubules
Phosphorylation of tau by glycogen synthase kinase 3β in intact mammalian cells influences the stability of microtubules
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DOI：
10.1016/s0304-3940(01)02206-6
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发表时间：
2001-10
影响因子：
2.5
通讯作者：
Huachun Sang;Zhonghua Lu;Yulong Li;B. Ru;Wenqing Wang;Jianguo Chen
中科院分区：
文献类型：
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作者：
Huachun Sang;Zhonghua Lu;Yulong Li;B. Ru;Wenqing Wang;Jianguo Chen
Tau是一种神经元微管相关蛋白，主要存在于轴突中。Tau的过度磷酸化降低了微管的稳定性，这可能是阿尔茨海默病的致病机制之一。为了了解tau蛋白和糖原合成酶激酶3β(GSK-3β)磷酸化tau蛋白对微管组织和稳定性的不同影响，我们利用增强型绿色荧光蛋白-tau(eGFP-tau)和GSK-3β对3T3细胞进行了转染研究，以定量微管的稳定性。激光共聚焦显微镜观察发现，Tau和GSK-3β磷酸化Tau均可诱导出粗细的微管束。这些束看起来要么相对笔直，要么围绕细胞的圆周形成一个环。粗、细微管束均能抵抗秋水仙素诱导的解离，其中粗微管束的抗性强于细微管束。GSK-3β磷酸化Tau诱导的细胞束对秋水仙碱敏感，并可被GSK-3β的抑制剂LiCl2逆转。
Tau is a neuronal microtubule-associated protein found predominantly in axons. Hyperphosphorylation of tau reduces the stability of microtubules, which may be a pathogenic mechanism in Alzheimer's disease. To understand the different effects between tau and glycogen synthase kinase 3β (GSK-3β) phosphorylated tau on the organization and stability of microtubules, we performed transfection studies on 3T3 cells using EGFP-tau (Enhanced Green Fluorescence Protein-tau) and GSK-3β to quantify the stability of microtubules. Laser confocal microscope observation revealed that thick and thin microtubule bundles could be induced by tau and GSK-3β phosphorylated tau. The bundles appeared either to be relatively straight or to form a ring around the circumference of the cell. Both the thick and thin microtubule bundles were resistant to colchicine-induced dissociation, with thick bundles more resistant than thin bundles. The bundles induced by GSK-3β phosphorylated tau were sensitive to colchicine, and could be reversed by the addition of LiCl, an inhibitor of GSK-3β.