The microtubule binding of tau and high molecular weight tau in apoptotic PC12 cells is impaired because of altered phosphorylation
The microtubule binding of tau and high molecular weight tau in apoptotic PC12 cells is impaired because of altered phosphorylation
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DOI：
10.1074/jbc.274.50.35686
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发表时间：
1999-12-10
影响因子：
4.8
通讯作者：
Johnson, GVW
中科院分区：
文献类型：
--
作者：
Davis, PK;Johnson, GVW
虽然微管网络在整个细胞生命过程中的重要性已经得到了很好的证实，但微管在细胞死亡过程中的动力学尚不清楚。在先前的研究中(Davis，P.K.和Johnson，G.V.(1999)Biochem)。J.340，51-58)，我们证明了微管相关蛋白tau的磷酸化在神经性PC12细胞凋亡过程中增加。这项研究的目的是确定在细胞凋亡过程中发生的tau磷酸化增加是否损害tau的微管结合能力。这项研究首次证明，在自然发生的细胞凋亡过程中，由于磷酸化的改变，tau和高分子量tan的微管结合显著受损。此外，共免疫荧光研究首次显示，在凋亡的神经细胞PC12细胞内的tau群体表现出不同的磷酸化。在对照的PC12细胞中，Tau-L染色(Tau-L识别非磷酸化的表位)贯穿整个细胞体。相反，Tau-L免疫反应在凋亡的PC12细胞中保留在核/核周围区域，但在细胞质直至质膜处显著减少。磷酸化tau蛋白在PC12细胞中的选择性分布表明，tau蛋白可能在细胞凋亡过程中的细胞骨架改变中起重要作用。
Although the importance of the microtubule network throughout cell life is well established, the dynamics of microtubules during apoptosis, a regulated cell death process, is unclear. In a previous study (Davis, P. K., and Johnson, G. V. (1999) Biochem. J. 340, 51-58) we demonstrated that the phosphorylation of the microtubule-associated protein tau was increased during neuronal PC12 cell apoptosis. The purpose of this study was to determine whether the increased tau phosphorylation that occurred during apoptosis impaired the microtubule binding capacity of tau. This study is the first demonstration that microtubule-binding by tau and high molecular weight tan is significantly impaired as a result of altered phosphorylation during a naturally occurring process, apoptosis. Furthermore, co-immunofluorescence studies reveal for the first time that tau populations within an apoptotic neuronal PC12 cell exhibit differential phosphorylation. In control PC12 cells, Tau-l staining (Tau-l recognizes an unphosphorylated epitope) is evident throughout the entire cell body. In contrast, Tau-l immunoreactivity in apoptotic PC12 cells is retained in the nuclear/perinuclear region but is significantly decreased in the cytoplasm up to the plasma membrane. The selective distribution of phosphorylated tau in apoptotic PC12 cells indicates that tau likely plays a significant role in the cytoskeletal changes that occur during apoptosis.