Biphasic Effect of Calcium Influx on Tau Phosphorylation: Phosphorylation: Biphasic Effect of Calcium Influx on Tau Phosphorylation: Involvement of Calcium-Dependent Phosphatase and Kinase Activities.

Conflicting data has emerged documenting decreased and increased levels of phospho-tau following calcium influx. Calcium influx achieved by treatment of SH-SY-5Y human neuroblastoma with 1 micro M calcium ionophore A23187 in the presence of 0.1 mM extracellular calcium depleted phospho-tau levels within 30 min. However, extending ionophore treatment to 60 min raised phospho-tau levels beyond that of control levels. Total tau levels were unchanged throughout these treatments, indicating that the reduction in PHF-1 reflected sequential alterations in tau phosphorylation rather than total tau. More rapid accumulation of phospho-tau accompanied treatment with increased concentrations of ionophore (3 micro M) and extracellular calcium (0.9 mM). An inhibitor active against calcium-dependent kinase(s) prevented the increase in phospho-tau following calcium influx. These data underscore that phospho-tau levels represent the summation of kinase and phosphatase activities and indicate that net dephosphorylation or phosphorylation is dependent upon the extent and/or rate of calcium influx