Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease.
Overexpression of tau protein inhibits kinesin-dependent trafficking of vesicles, mitochondria, and endoplasmic reticulum: implications for Alzheimer's disease.
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DOI：
10.1083/jcb.143.3.777
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发表时间：
1998-11-02
期刊：
影响因子：
--
通讯作者：
Mandelkow E
中科院分区：
文献类型：
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作者：
Ebneth A;Godemann R;Stamer K;Illenberger S;Trinczek B;Mandelkow E
神经元微管相关蛋白 tau 通过稳定轴突微管（作为运动蛋白驱动的运输过程的轨道），在建立细胞极性方面发挥着重要作用。为了研究 tau 在细胞内转运中的作用，我们研究了稳定转染的 CHO 细胞和分化的神经母细胞瘤 N2a 细胞中 tau 表达的影响。 Tau 蛋白会导致细胞形状发生变化，延缓细胞生长，并显着改变各种细胞器的分布，这些细胞器已知通过微管依赖性运动蛋白进行运输。线粒体无法转运到周围细胞区室并聚集在微管组织中心附近。内质网变得不那么致密并且不再延伸到细胞外围。在分化的 N2a 细胞中，tau 蛋白的过度表达导致神经突中线粒体的消失。这些效应是由于 tau 蛋白与微管结合并通过优先损害由驱动蛋白样运动蛋白介导的正端定向运输而减慢细胞内运输而引起的。由于在阿尔茨海默氏病中，tau 蛋白升高且定位错误，因此这些观察结果指出了神经元逐渐退化的可能原因。
The neuronal microtubule-associated protein tau plays an important role in establishing cell polarity by stabilizing axonal microtubules that serve as tracks for motor-protein–driven transport processes. To investigate the role of tau in intracellular transport, we studied the effects of tau expression in stably transfected CHO cells and differentiated neuroblastoma N2a cells. Tau causes a change in cell shape, retards cell growth, and dramatically alters the distribution of various organelles, known to be transported via microtubule-dependent motor proteins. Mitochondria fail to be transported to peripheral cell compartments and cluster in the vicinity of the microtubule-organizing center. The endoplasmic reticulum becomes less dense and no longer extends to the cell periphery. In differentiated N2a cells, the overexpression of tau leads to the disappearance of mitochondria from the neurites. These effects are caused by tau's binding to microtubules and slowing down intracellular transport by preferential impairment of plus-end–directed transport mediated by kinesin-like motor proteins. Since in Alzheimer's disease tau protein is elevated and mislocalized, these observations point to a possible cause for the gradual degeneration of neurons.