Phosphatase inhibition in human neuroblastoma cells alters tau antigenicity and renders it incompetent to associate with exogenous microtubules
Abstract
The abnormal cytoskeletal organization observed in Alzheimer's disease has been suggested to arise from hyperphosphorylation of tau and the resultant elimination of its ability to associate with microtubules. This possibility has been supported by a number of studies under cell-free conditions utilizing various kinases, phosphatases and their corresponding inhibitors each, and by treatment of intact cells with kinase and phosphatase activators and inhibitors. However, in studies utilizing intact cells, it remained difficult to attribute microtubule compromise specifically to tau hyperphosphorylation due to potential influence of inhibitors on tubulin and/or other microtubule-associated proteins which themselves possess assembly-regulatory phosphorylation sites. To address this difficulty, we subjected SH-SY-5Y human neuroblastoma cells to treatment with the phosphatase inhibitor okadaic acid (OA), which has been previously demonstrated to depolymerize microtubules in these cells. OA induced an increase in tau hyperphosphorylation as evidenced by an increase in Alz-50 immunoreactivity and a corresponding decrease in Tau-1 immunoreactivity. When tau-enriched fractions from OA-treated cells were incubated under microtubule assembl...Continue Reading
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