Rho A participates in the regulation of phosphatidylserine-dependent procoagulant activity at the surface of megakaryocytic cells.
Once exposed at the external surface of activated platelets or apoptotic cells, phosphatidylserine, an anionic phospholipid mostly sequestered in the inner leaflet of the plasma membrane, plays essential roles in hemostasis and phagocytosis. The mechanism governing the migration of the phosphatidylserine to the exoplasmic leaflet is not yet fully understood. We have proposed that store-operated calcium entry (SOCE) constitutes a key step of this process. ERK pathway is among the elements modulating SOCE and phosphatidylserine externalization in megakaryocytic HEL cells. Here, we investigated the role of small GTPase Rho A, which may interact with the ERK pathway. Specific inhibitors of Rho A (exoenzyme C3 and toxin B) reduced both SOCE and phosphatidylserine-dependent procoagulant activity. Simultaneous inhibition of Rho A and extracellular signal-regulated kinase (ERK) pathways did not elicit further reduction with respect to each individual one. Rho A can regulate SOCE and phosphatidylserine exposure through the reorganization of actin cytoskeleton, but not through ROCK pathway. Hence, Rho A is another regulatory element for the completion of SOCE-induced phosphatidylserine transmembrane redistribution in HEL cells.
Kunzelmann
C
C
Institut d'Hématologie et d'Immunologie, Université Louis Pasteur, Faculté de Médecine, Strasbourg, France.
Freyssinet
J-M
JM
Martínez
M C
MC
D002118:Calcium / Q000032:analysis / Q000378:metabolism; D020013:Calcium Signaling; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000502:physiology / Q000648:ultrastructure; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006487:Hemostasis; D006801:Humans; D008533:Megakaryocytes / Q000378:metabolism / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology; D010718:Phosphatidylserines / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000502:physiology*
D004791:Enzyme Inhibitors; D010718:Phosphatidylserines; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D020742:rhoA GTP-Binding Protein; D002118:Calcium