Formation and Function of Weibel-Palade Bodies

Weibel-Palade bodies (WPBs) are secretory organelles used for post-synthesis storage in endothelial cells that can, very rapidly, be triggered to release their contents. They carry a variety of bioactive molecules that are needed to mount a rapid response to the complex environment of cells that line blood vessels. They store factors that are essential to haemostasis and inflammation, as well as factors that modulate vascular tonicity and angiogenesis. The number of WPBs and their precise content vary between endothelial tissues, reflecting their differing physiological circumstances. The particular functional demands of the highly multimerised haemostatic protein von Willebrand Factor (VWF), which is stored in WPBs as tubules until release, are responsible for the cigar shape of these granules. How VWF tubules drive the formation of these uniquely shaped organelles, and how WPB density increases during maturation, has recently been revealed by EM analysis using high-pressure freezing and freeze substitution. In addition, an AP1/clathrin coat has been found to be essential to WPB formation. Following recruitment of cargo at the TGN, there is a second wave of recruitment that delivers integral and peripheral membrane proteins to WPBs, some of which is AP3 dependent.