Thesis defense Ellie Karampini

Weibel-Palade Body Formation and Release: an Odyssey through the Secretory Pathway

On  24 April 2020 (13:00) Ellie Karampini defended her thesis 'Weibel-Palade Body Formation and Release: an Odyssey through the Secretory Pathway' at the University of Amsterdam

Prof J Voorberg PhD
R Bierings PhD

online defense without public

In vesicular trafficking, organelle biogenesis and maturation, as well as organelle secretion, vesicle membranes fuse with their targets for content delivery. These fusion steps are universally governed by Soluble N–ethylmaleimide sensitive factor (NSF) attachment protein receptor (SNARE) proteins. SNARE proteins interact with each other in a complex formation of a four-helix bundle, consisting of one helix from the v- and three helices from t-SNAREs (chapter 4). The main purpose of this study is to provide insight into the regulation of biogenesis of WPBs from the trans Golgi network. In addition, we explored how additional cargo is being distributed to preformed WPBs and how these fully mature LROs subsequently deliver their hemostatic, inflammatory and angiogenic content in the vascular lumen. In chapter 2 we provide an overview of the recent developments on the mechanisms that drive the biogenesis and maturation of LROs focusing on platelet α- and δ-granules, and endothelial cell WPBs. We continue by discussing the role of the ER-to-Golgi SNARE Sec22b in anterograde protein trafficking and WPB biogenesis (chapter 3). In chapter 4, we identify the interactome of Sec22b in ECs and evaluate the role of its binding partner STX5 in WPB formation. Next, we review recent advances in WPB exocytosis, including stimulus-dependent cascades and known exocytotic machinery (chapter 5). In chapter 6 we discuss in depth the mechanisms underlying AP-3 dependent WPB maturation and how this pathway affects WPB exocytosis. In chapter 7 we reveal the role of a newly discovered SNARE present on WPBs (STX3) in stimulus-induced WPB exocytosis. Finally, we summarize and discuss our finding in chapter 8 and provide directions for future research.