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 occurs in cells fulfilling a more specialized function, such as the phosphatidylserine-dependent procoagulant response of platelets after appropriate activation. Although an increase in cytoplasmic Ca2+ is essential to trigger the remodeling of the plasma membrane, little is known about intracellular signals leading to phosphatidylserine externalization. Here, the role of store-operated Ca2+ entry on phosphatidylserine exposure was investigated in human erythroleukemia HEL cells, a pluripotent lineage with megakaryoblastic properties. Ca2+ entry inhibitors (SKF-96365, LaCl(3), and miconazole) inhibited 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 pretreated with cytochalasin D, an agent that disrupts the microfilament network of the cytoskeleton, store-operated Ca2+ entry and phosphatidylserine externalization at the cell surface were inhibited. In a context where most of the key actors remain to be identified, these results provide evidence for the implication of both store-operated Ca2+ entry and cytoskeleton architectural organization in the regulation of phosphatidylserine transbilayer migration.
Kunzelmann-Marche
C
C
Institut d'Hématologie et d'Immunologie, Université Louis Pasteur, Faculté de Médecine, 4 rue Kirschleger, Strasbourg 67085, France.
Freyssinet
J M
JM
Martínez
M C
MC
D000199:Actins / Q000502:physiology*; D017304:Annexin A5 / Q000737:chemistry; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D003599:Cytoskeleton / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007811:Lanthanum / Q000494:pharmacology; D008051:Lipid Bilayers / Q000378:metabolism; D008825:Miconazole / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000199:Actins; D017304:Annexin A5; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008051:Lipid Bilayers; D010718:Phosphatidylserines; C028521:lanthanum chloride; D015638:Cytochalasin D; D019284:Thapsigargin; D007811:Lanthanum; D008825:Miconazole; C063159:1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole; D002118:Calcium