Weibel−Palade bodies at a glance

Abstract

The vascular environment can rapidly alter, and the speed with which responses to both physiological and pathological changes are required necessitates the existence of a highly responsive system. The endothelium can quickly deliver bioactive molecules by regulated exocytosis of its secretory granules, the Weibel-Palade bodies (WPBs). WPBs include proteins that initiate both haemostasis and inflammation, as well those that modulate blood pressure and angiogenesis. WPB formation is driven by von Willebrand factor, their most abundant protein, which controls both shape and size of WPBs. WPB are generated in a range of sizes, with the largest granules over ten times the size of the smallest. In this Cell Science at a Glance and the accompanying poster, we discuss the emerging mechanisms by which WPB size is controlled and how this affects the ability of this organelle to modulate haemostasis. We will also outline the different modes of exocytosis and their polarity that are currently being explored, and illustrate that these large secretory organelles provide a model for how elements of secretory granule biogenesis and exocytosis cooperate to support a complex and diverse set of functions.

Direct trafficking pathways from the Golgi apparatus to the plasma membrane

“…Clathrin carriers range from the typical spherical 60-100 nm clathrin-coated vesicles to larger, up to 1200 nm in size, grape-like structures displaying several coated buds [68]. The clathrin coat and its accessory protein complex, AP-1, was also shown to drive the formation of Weibel-Palade bodies, large cigar-shaped secretory organelles produced by endothelial cells which can be up to 5 μm long [69,70]. It has been proposed that the diverse array of carrier morphologies could be an adaptive mechanism for a variety cargo size or abundance.…”

A sticky proposition: The endothelial glycocalyx and von Willebrand factor

“…How exactly blood flow fits into the different pathways of VWF secretion is unclear. However, it is thought that under physiological conditions, the shear stress generated by flowing blood against the intact vasculature may be involved in regulating the continuous basal secretion of VWF from the endothelium . In this context, the mechanotransductive properties of the EGC could certainly play a critical role in establishing an individual's baseline plasma VWF levels.…”

“…However, it is thought that under physiological conditions, the shear stress generated by flowing blood against the intact vasculature may be involved in regulating the continuous basal secretion of VWF from the endothelium. 2 Alternatively, the role of the EGC in VWF secretion could also be considered in the context of angiogenesis. Recently, VWF has been implicated in this process as an inhibitory regulator, supported by evidence of angiodysplastic vascular malformations that are sometimes observed in von Willebrand disease patients.…”

“…EC‐derived VWF can be released via three pathways: regulated, constitutive, or basal. During regulated VWF secretion, agonists such as histamine and epinephrine can stimulate acute WPB exocytosis through calcium‐ or cyclic adenosine monophosphate‐dependent mechanisms, respectively . In contrast, constitutive VWF secretion is mediated by premature WPBs and occurs predominantly on the basolateral aspect of ECs .…”

“…During regulated VWF secretion, agonists such as histamine and epinephrine can stimulate acute WPB exocytosis through calcium-or cyclic adenosine monophosphate-dependent mechanisms, respectively. 1,2 In contrast, constitutive VWF secretion is mediated by premature WPBs and occurs predominantly on the basolateral aspect of ECs. 1 Last, continuous basal VWF secretion from WPBs into the vessel lumen is recognized to be the principal determinant of an individual's baseline plasma VWF levels.…”