Submitted June 25, 2008
Accepted October 2, 2008
Phospholipase D1 is specifically required for regulated secretion of von-Willebrand factor from endothelial cells
Jennifer Disse, Nicolas Vitale, Marie-France Bader, and Volker Gerke*
Institute of Medical Biochemistry, Centre for Molecular Biology of Inflammation, University of Munster, Munster, Germany
Institut des Neurosciences Cellulaires et Integratives UMR-7168, CNRS & Universite Louis Pasteur, Strasbourg, France
* Corresponding author; email: gerke{at}uni-muenster.de.
Endothelial cells regulate thrombosis, haemostasis and inflammatory responses by supplying the vasculature with a number of factors that include pro-coagulant von-Willebrand factor (vWF) and fibrinolytic tissue-type plasminogen activator (tPA). Both proteins can be secreted in a Ca2+-regulated manner following endothelial activation but exhibit opposing physiological effects. In search for factors that could modulate endothelial responses by selectively affecting the secretion of pro- or anti-coagulant proteins we identify here phospholipase D1 (PLD1) as a specific regulator of vWF secretion. PLD1 is translocated to the plasma membrane upon stimulation of endothelial secretion and this process correlates with the generation of phosphatidic acid (PA) in the plasma membrane. Histamine-evoked secretion of vWF, but not tPA, is inhibited by blocking PLD-mediated production of PA and this effect can be attributed to PLD1 and not PLD2. Thus, different mechanisms appear to control the agonist induced secretion of vWF and tPA, with only the former requiring PLD1.
