Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of von Willebrand factor secretion

摘要

Vascular endothelial cells react to local perturbations such as tissue inflammation or vascular injury by the acute secretion of factors that control coagulation and leukocyte, as well as platelet adhesion. Many of these factors are stored in specialized secretory granules, Weibel-Palade bodies (WPB), that undergo exocytosis after endothelial activation. WPB are elongated structures1 that form at the trans-Golgi network and further mature during their microtubule-dependent transport to the cell periphery.2 Major WPB constituents are the coagulation-promoting von Willebrand factor (VWF) that forms condensely packed tubules within WPB, the leukocyte receptor P-selectin, and the tetraspanin CD63 (Lamp3) that is acquired from the endosomal system during WPB maturation.3'4