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

Abstract

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 µM 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 µM) 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