Significance of Capacitative Ca2+Entry in the Regulation of Phosphatidylserine Expression at the Surface of Stimulated Cells

Abstract

The transverse redistribution of plasma membrane phosphatidylserine is one of the hallmarks of cells undergoing apoptosis and also occurs in cells fulfilling a more specialized function, such as platelets after appropriate activation. Although an increase in intracellular Ca²⁺ is required to trigger the remodeling of the plasma membrane, little information regarding intracellular signals leading to phosphatidylserine externalization has been provided. Scott syndrome is an extremely rare inherited disorder of the migration of phosphatidylserine toward the exoplasmic leaflet of the plasma membrane of stimulated blood cells. We have studied here the intracellular Ca²⁺ mobilization and Ca²⁺ entry involved in tyrosine phosphorylation in Epstein Barr virus (EBV)-infected B cells derived from a patient with Scott syndrome, her daugther, and control subjects. An alteration of Ca²⁺ entry through the plasma membrane and subsequent tyrosine phosphorylation induced by Ca²⁺ were observed in Scott EBV-B cells, but the release of Ca²⁺ from intracellular stores was normal. Furthermore, phosphatidylserine externalization at the surface of stimulated cells does not depend on tyrosine kinases. These results suggest that the defect of phosphatidylserine exposure in Scott syndrome cells is related to the alteration of a particular way of Ca²⁺ entry, referred to as capacitative Ca²⁺ entry, although some differences may be related to the cell type. Hence, this genetic mutant testifies to the prime significance of Ca²⁺ signaling in the regulation of phosphatidylserine expression at the surface of stimulated cells.