MRC National Institute for Medical Research, London
Science for Health
Matthew Hannah group
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Secretory vesicle formation in human endothelial cells
Secretory vesicles are microscopic, membrane-bound compartments found inside cells that are essential for communication between cells and their environment. They are used to transport soluble biological signalling molecules such as enzymes, hormones or neurotransmitters out of the cell and they also deliver membrane proteins such as receptors or transporters to the cell surface. We study the formation of secretory vesicles in human endothelial cells grown in culture, focusing mostly on the Weibel-Palade body (WPB) a distinctive endothelial-cell specific secretory vesicle, responsible for the storage and stimulationdependent release of von Willebrand factor (VWF) a protein involved in blood clotting. Analysis of this process will increase our understanding of cardiovascular biology and cellular secretory processes in general.
We have recently carried out a kinetic analysis of the biosynthesis, storage and secretion of VWF in our cells using a metabolic labelling approach. Contrary to previously published work, we found that VWF was very efficiently sorted into regulated secretory vesicles, but these were not efficiently stored due to spontaneous, non-stimulated secretion.
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Weibel-Palade bodies and Golgi apparatus visualised in a cultured human endothelial cell.
Selected publications
- Berriman, JA; Li, S; Hewlett, LJ; Wasilewski, S; Kiskin, FN; Carter, T; Hannah, MJ and Rosenthal, PB (2009)
Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells.
Proceedings of the National Academy of Sciences of the United States of America 106, 17407-17412 PubMed abstract - Giblin, JP; Hewlett, LJ and Hannah, MJ (2008)
Basal secretion of von Willebrand factor from human endothelial cells.
Blood 112, 957-964 PubMed abstract - Hannah, MJ; Skehel, P; Erent, M; Knipe, L; Ogden, D and Carter, T (2005)
Differential kinetics of cell surface loss of von Willebrand factor and its propolypeptide after secretion from Weibel-Palade bodies in living human endothelial cells.
Journal of Biological Chemistry 280, 22827-22830 PubMed abstract
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