The microtubule binding of tau and high molecular weight tau in apoptotic PC12 cells is impaired because of altered phosphorylation

Although the importance of the microtubule network throughout cell life is well established, the dynamics of microtubules during apoptosis, a regulate d cell death process, is unclear. In a previous study (Davis, P. K., and Jo hnson, G. V. (1999) Biochem. J. 340, 51-58) we demonstrated that the phosph orylation of the microtubule-associated protein tau was increased during ne uronal PC12 cell apoptosis. The purpose of this study was to determine whet her the increased tau phosphorylation that occurred during apoptosis impair ed the microtubule binding capacity of tau. This study is the first demonst ration that microtubule-binding by tau and high molecular weight tan is sig nificantly impaired as a result of altered phosphorylation during a natural ly occurring process, apoptosis. Furthermore, co-immunofluorescence studies reveal for the first time that tau populations within an apoptotic neurona l PC12 cell exhibit differential phosphorylation. In control PC12 cells, Ta u-l staining (Tau-l recognizes an unphosphorylated epitope) is evident thro ughout the entire cell body. In contrast, Tau-l immunoreactivity in apoptot ic PC12 cells is retained in the nuclear/perinuclear region but is signific antly decreased in the cytoplasm up to the plasma membrane. The selective d istribution of phosphorylated tau in apoptotic PC12 cells indicates that ta u likely plays a significant role in the cytoskeletal changes that occur du ring apoptosis.