Secreting von Willebrand factor in a Gα-SNAP.

In this issue of Blood, Rusu et al use a state-of-the-art combination of pharmacological, genetic, and molecular techniques to dissect a mechanism for von Willebrand factor (vWF) secretion from endothelial cells mediated via Gaq/11 and Ga12 that can be triggered in basal or stimulated conditions. Indeed, although the storage of vWF in Weibel-Palade bodies (WPBs) of endothelial cells has been known for decades, the molecular mechanisms governing WPB docking with plasma membrane and vWF secretion remains undefined. One of the reasons this is still a very active area of investigation is that understanding the mechanism behind WPB docking is crucial for understanding potential pharmacological targets for pathological conditions associated with platelet aggregation/thrombi (e.g., stroke), where vWF levels directly correlate with severity of disease progress. The work by Rusu et al opens up a new area of investigation into G-protein-coupled receptors as triggers for WPB fusion at the plasma membrane and for vWF secretion.