Deciphering the plasma membrane hallmarks of apoptotic cells: Phosphatidylserine transverse redistribution and calcium entry

Taking advantage of these mutant lymphoblastoid B cells, we have studied the relationship between this mode of Ca2+ entry and phosphatidylserine redistribution during apoptosis. Ca2+ ionophore induced apoptosis in Scott but not in control cells. However, inhibition of store-operated Ca2+ channels led to caspase-independent DNA fragmentation and decrease of mitochondrial membrane potential in both control and Scott cells. Inhibition of cytochrome P450 also reduced capacitative Ca2+ entry and induced apoptosis at comparable extents in control and Scott cells. During the apoptotic process, both control and more markedly Scott cells externalized phosphatidylserine, but in the latter, this membrane feature was however dissociated from several other intracellular changes.The present results suggest that different mechanisms account for phosphatidylserine transmembrane migration in cells undergoing stimulation and programmed death. These observations testify to the plasticity of the plasma membrane remodeling process, allowing normal apoptosis even when less fundamental functions are defective.During apoptosis, changes in cytosolic Ca2+ are likely to play a critical role by triggering the activation of Ca2+-dependent events inducing global intracellular and morphological modifications [1,2]. Among these changes, early transverse redistribution of plasma membrane phosphatidylserine is one of the well-documented hallmarks of cells undergoing apoptosis [3,4], and has been shown to depend on caspase-3 protease activity [5] and cytoplasmic Ca2+ concentration [6,7]. The resulting exposure of phosphatidylserine in the outer leaflet may serve as a recognition signal for phagocytosis of senescent cells to be rapidly cleared [3,8-10]. Phosphatidylserine is also essential for the assembly of the blood coagulation enzyme complexes at the surface of stimulated specialized cells such as platelets, as demonstrated by hemorrhages in Scott syndrome, an extremely rare inherited bleeding dis