Weibel Palade Body formation and release

On 24 April 2020 Ellie Karampini defended her thesis at the University of Amsterdam. Due to the Corana regulations the defense took place online, without public. 

Ellie provides insight into the regulation of biogenesis of WPBs from the trans Golgi network. In addition, she explored how additional cargo is being distributed to preformed WPBs and how these fully mature LROs (lysosome-related organelles)  subsequently deliver their hemostatic, inflammatory and angiogenic content in the vascular lumen.

The online defense. Ellie Karampini in upper left corner.

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.

In her thesis Ellie brings 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. She discusses the role of the ER-to-Golgi SNARE Sec22b in anterograde protein trafficking and WPB biogenesis.

In addition, Ellie identified the interactome of Sec22b in ECs and evaluated the role of its binding partner STX5 in WPB formation. Next, she reviewed recent advances in WPB exocytosis, including stimulus-dependent cascades and known exocytotic machinery.

She further discusses in depth the mechanisms underlying AP-3 dependent WPB maturation and how this pathway affects WPB exocytosis and reveals the role of a newly discovered SNARE present on WPBs (STX3) in stimulus-induced WPB exocytosis.

Promotor:
Prof J Voorberg PhD
Copromotor:
R Bierings PhD

Venue: 
online defense