Molecular mechanisms involved in Weibel-Palade body exocytosis

ndothelial cells form the barrier between the circulating blood and the underlying tissue. Endothelial cells contain specialized organelles called Weibel-Palade bodies that contain proteins involved in blood coagulation and inflammatory processes. In this thesis we describe a studies unraveling the molecular mechanisms involved in Weibel-Palade body exocytosis.
By use of a combination of cell biological and mass-spectrometry based techniques, we identified a couple of new regulators involved in the regulation of Weibel-Palade body exocytosis. We show that Epac1 and Rap1 are involved in cAMP mediated secretion of Weibel-Palade bodies. By use of mass-spectrometry we identified candidates possibly binding to Rap1. We identified Rap1 as a possible downstream target of Rap1. PREX-1 is involved in the activation of the small GTPase Rac1. We show in that both PREX-1 and Rac1 are involved in epinephrine induced secretion of Weibel-Palade bodies.