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 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 tau 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-1 staining (Tau-1 recognizes an unphosphorylated epitope) is evident throughout the entire cell body. In contrast, Tau-1 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.
Davis
P K
PK
Department of Pharmacology, University of Alabama at Birmingham, Birmingham, Alabama 35294-0017, USA.
Johnson
G V
GV
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D002843:Chromatin / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005455:Fluorescent Antibody Technique; D008870:Microtubules / Q000378:metabolism*; D008970:Molecular Weight; D009414:Nerve Growth Factors / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000502:physiology; D016716:PC12 Cells; D017239:Paclitaxel / Q000494:pharmacology; D010766:Phosphorylation; D051381:Rats; D014404:Tubulin / Q000187:drug effects / Q000378:metabolism*; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
D002843:Chromatin; D009414:Nerve Growth Factors; D014404:Tubulin; D016875:tau Proteins; D017239:Paclitaxel