In our group we study the mechanism of exocytosis of Weibel-Palade bodies (WPB’s). These unique storage organelles in vascular endothelial cells deliver inflammatory and haemostatic mediators to the vascular lumen in response to agonists like thrombin and vasopressin. The main component of WPB’s is von Willebrand factor (VWF), a multimeric glycoprotein crucial for platelet plug formation. Stimulation with agonists causes exocytosis of WPB’s by a translocation of these organelles to and fusion with the plasma membrane. However, the exact mechanism of fusion of WPB’s with the plasma membrane is not yet elucidated.
Membrane fusion is mediated by the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex. This complex consisting of syntaxin, synaptosomal-associated protein (SNAP), and vesicle-associated membrane protein (VAMP) mediates fusion of vesicles with target membranes. It is reported that the formation of the SNARE complex can be regulated by syntaxin binding proteins including Munc18 proteins. In a proteomic profiling of WPB’s we detected syntaxin binding protein 4 (STXBP4) as a novel potentially regulator of WPB’s release. Furthermore, SNPs in syntaxin binding protein 5 (STXBP5) have been related to a higher VWF-plasma level in blood.
In the current project we study the function of different syntaxin binding proteins in the regulation of WPB release. In this subproject we will focus on the elucidation of the functional role of STXBP4 and STXBP5 in exocytosis of WPB’s.
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