title: 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 daughter, 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.
authors.affiliation: Institut d'Hématologie et d'Immunologie, Faculté de Médecine, Université Louis Pasteur, Strasbourg, France.
authors.forename: M C
authors.initials: MC
authors.lastname: Martínez
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: F
authors.initials: F
authors.lastname: Toti
authors.forename: E
authors.initials: E
authors.lastname: Fressinaud
authors.forename: J
authors.initials: J
authors.lastname: Dachary-Prigent
authors.forename: D
authors.initials: D
authors.lastname: Meyer
authors.forename: J M
authors.initials: JM
authors.lastname: Freyssinet
mesh_terms: D000368:Aged; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D001778:Blood Coagulation Disorders / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D008213:Lymphocyte Activation; D010718:Phosphatidylserines / Q000096:biosynthesis*; D010743:Phospholipids / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D013577:Syndrome; D019284:Thapsigargin / Q000494:pharmacology; D014443:Tyrosine / Q000378:metabolism
chemical_list: D015220:Calcium Channels; D004791:Enzyme Inhibitors; D010718:Phosphatidylserines; D010743:Phospholipids; D000001:Calcimycin; D014443:Tyrosine; D019284:Thapsigargin; D019833:Genistein; D011505:Protein-Tyrosine Kinases