MITOTIC PHOSPHORYLATION OF TAU-PROTEIN IN NEURONAL CELL-LINES RESEMBLES PHOSPHORYLATION IN ALZHEIMERS-DISEASE

Tau protein, a neuronal microtubule-associated protein is phosphorylat ed on several sites when extracted from brain tissue and is a substrat e for many protein kinases in vitro. In Alzheimer's disease it becomes hyperphosphorylated, notably at Ser-Pro or Thr-Pro motifs, and forms the paired helical filaments (PHFs). The increased phosphorylation ran be detected by several antibodies raised against Alzheimer tau. We sh ow here that a similar type of phosphorylation can be observed in cell s of neuronal origin during mitosis. Murine neuroblastoma cells (N2a) were stably transfected with htau40, the largest of the six human tau isoforms in the brain. We used several antibodies reporting on the sta te of phosphorylation of tau (Tau-l, AT8, AT180, PHF-1, and T46) and t he antibody MPM-2 that recognizes phosphorylated mitotic proteins. The results show that tau is in a state of low phosphorylation in interph ase cells, whereas during mitosis it becomes highly phosphorylated. Th is behavior was also found for endogenous tan protein in human neurobl astoma cells (LAN-5). The similarity between tau phosphorylation in di viding neuronal cells and Alzheimer degenerating neurons may indicate that aging neurons exposed to inappropriate signals respond by an atte mpt to activate their machinery for regeneration.