Regulation of phosphatidylserine transbilayer redistribution by store-operated Ca2+ entry - Role of actin cytoskeleton

The phosphatidylserine transmembrane redistribution at the cell surface is one of the early characteristics of cells undergoing apoptosis and also occ urs in cells fulfilling a more specialized function, such as the phosphatid ylserine-dependent procoagulant response of platelets after appropriate act ivation. Although an increase in cytoplasmic Ca2+ is essential to trigger t he remodeling of the plasma membrane, little is known about intracellular s ignals leading to phosphatidylserine externalization, Here, the role of sto re-operated Ca2+ entry on phosphatidylserine exposure was investigated in h uman erythroleukemia HEL cells, a pluripotent lineage with megakaryoblastic properties. Ca2+ entry inhibitors (SKF-96365, LaCl3, and miconazole) inhib ited store-operated Ca2+ entry in A23187- or thapsigargin-stimulated cells and reduced the degree of phosphatidylserine externalization concomitantly, providing evidence for a close link between the two processes. In cells pr etreated with cytochalasin D, an agent that disrupts the microfilament netw ork of the cytoskeleton, store-operated Ca2+ entry and phosphatidylserine e xternalization at the cell surface were inhibited, In a context where most of the key actors remain to be identified, these results provide evidence f or the implication of both store-operated Ca2+ entry and cytoskeleton archi tectural organization in the regulation of phosphatidylserine transbilayer migration.