Lifecycle of Weibel-Palade bodies

2017 ◽  
Vol 37 (01) ◽  
pp. 13-24 ◽  
Author(s):  
Marjon Mourik ◽  
Jeroen Eikenboom
Keyword(s):  
Golgi Apparatus ◽  
Signaling Pathways ◽  
Von Willebrand Factor ◽  
Vascular Endothelium ◽  
Regulated Secretion ◽  
Secretion Pathway ◽  
Main Component ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryWeibel-Palade bodies (WPBs) are rod or cigar-shaped secretory organelles that are formed by the vascular endothelium. They contain a diverse set of proteins that either function in haemostasis, inflammation, or angiogenesis. Biogenesis of the WPB occurs at the Golgi apparatus in a process that is dependent on the main component of the WPB, the haemostatic protein von Willebrand Factor (VWF). During this process the organelle is directed towards the regulated secretion pathway by recruiting the machinery that responds to exocytosis stimulating agonists. Upon maturation in the periphery of the cell the WPB recruits Rab27A which regulates WPB secretion. To date several signaling pathways have been found to stimulate WPB release. These signaling pathways can trigger several secretion modes including single WPB release and multigranular exocytosis. In this review we will give an overview of the WPB lifecycle from biogenesis to secretion and we will discuss several deficiencies that affect the WPB lifecycle.

scholarly journals Actomyosin II contractility expels von Willebrand factor from Weibel–Palade bodies during exocytosis

2011 ◽  
Vol 194 (4) ◽  
pp. 613-629 ◽  
Author(s):  
Thomas D. Nightingale ◽  
Ian J. White ◽  
Emily L. Doyle ◽  
Mark Turmaine ◽  
Kimberly J. Harrison-Lavoie ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Secretory Granules ◽  
Myosin Ii ◽  
Human Endothelial Cells ◽  
Spatiotemporal Resolution ◽  
Regulated Secretion ◽  
Experimental Systems ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Extracellular Environment

The study of actin in regulated exocytosis has a long history with many different results in numerous systems. A major limitation on identifying precise mechanisms has been the paucity of experimental systems in which actin function has been directly assessed alongside granule content release at distinct steps of exocytosis of a single secretory organelle with sufficient spatiotemporal resolution. Using dual-color confocal microscopy and correlative electron microscopy in human endothelial cells, we visually distinguished two sequential steps of secretagogue-stimulated exocytosis: fusion of individual secretory granules (Weibel–Palade bodies [WPBs]) and subsequent expulsion of von Willebrand factor (VWF) content. Based on our observations, we conclude that for fusion, WPBs are released from cellular sites of actin anchorage. However, once fused, a dynamic ring of actin filaments and myosin II forms around the granule, and actomyosin II contractility squeezes VWF content out into the extracellular environment. This study therefore demonstrates how discrete actin cytoskeleton functions within a single cellular system explain actin filament–based prevention and promotion of specific exocytic steps during regulated secretion.

Desmopressin testing in children with von Willebrand syndrome in haemostaseologic centers of Saxonia, Saxonia-Anhalt and Thuringia

2009 ◽  
Vol 29 (S 01) ◽  
pp. S98-S102 ◽  
Author(s):  
B. Huhn ◽  
A. Hofmann ◽  
K. Hofmann ◽  
H. Sirb ◽  
V. Aumann ◽  
...  
Keyword(s):  
Partial Response ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Vascular Endothelium ◽  
Test Performance ◽  
Coagulation Factor ◽  
Syndrome Type ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe influence of desmopressin on hemostasis is mediated by the release of von Willebrand factor and of coagulation factor VIII from vascular endothelium. The necessity of testing desmopressin effectiveness on hemostasis is a matter of controversy and the performance of the test is not yet standardized. For this reason the desmopressin tests in 114 children with von Willebrand syndrome (type 1, n=98; type 2A, n=12; type 2M, n=2; type 2N, n=2) carried out in 7 paediatric haemostaseologic centers were retrospectively analyzed. The effectiveness of desmopressin was assessed using defined response criteria. As expected, the test performance showed a wide variation among the centers. In 99 children desmopressin was given intravenously as a short infusion at a dosage ranging from 0.25 to 0.41 μg/kg and in 15 intranasally at an absolute dose of 40 to 300 μg. The points of time for blood taking after desmopressin application ranged from 0.5 to 12 h. The absent desmopressin response in 7 patients (6%) and the partial response in 15 indicate the necessity of testing desmopressin effectiveness before the first therapeutic use. The application of desmopressin was well tolerated by the patients.

Adenosine 3’:5’-Cyclic Monophosphate Induces Regulated Secretion of Tissue-Type Plasminogen Activator and von Willebrand Factor from Cultured Human Endothelial Cells

1998 ◽  
Vol 79 (04) ◽  
pp. 853-858 ◽  
Author(s):  
R. J. Hegeman ◽  
van den Eijnden-Schrauwen ◽  
J. J. Emeis
Keyword(s):  
Endothelial Cells ◽  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Tissue Type ◽  
Tissue Type Plasminogen Activator ◽  
Regulated Secretion ◽  
Cyclic Monophosphate ◽  
Type Plasminogen Activator ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe effect of compounds increasing intracellular adenosine 3’:5’-cyclic monophosphate [cAMP]i levels (prostacyclin, isoproterenol, forskolin, cholera toxin), and of the cAMP analogs 8-bromo-cAMP and dibutyryl-cAMP, on the regulated secretion (acute release) of tissue-type plasminogen activator (tPA) and von Willebrand factor (vWF) was studied in cultured human umbilical vein endothelial cells (HUVEC).Prostacyclin, isoproterenol and forskolin, which increased [cAMP]i in HUVEC, and the cell-permeant cAMP analog 8-bromo-cAMP induced dose- and time-dependent secretion of tPA and vWF. The extent of vWF and tPA release correlated with [cAMP]i, and was increased by the phosphodiesterase inhibitor isobutylmethylxanthine.In contrast to thrombin, the cAMP-elevating agents did not increase the intracellular calcium concentration [Ca2+]i in HUVEC. At sub-maximal concentrations, the effects of thrombin and prostacyclin were additive.Our results show that an increase in [cAMP]i resulted in regulated secretion (acute release) of tPA and vWF from HUVEC, without the concomitant increase in [Ca2+]i which is, in HUVEC, essential for thrombin-induced regulated secretion to occur. cAMP-induced secretion represents a novel mechanism for causing regulated secretion of tPA and vWF from endothelial cells.

scholarly journals Fluvastatin inhibits regulated secretion of endothelial cell von Willebrand factor in response to diverse secretagogues

2007 ◽  
Vol 405 (3) ◽  
pp. 597-604 ◽  
Author(s):  
Richard J. Fish ◽  
Hong Yang ◽  
Christelle Viglino ◽  
Raoul Schorer ◽  
Sylvie Dunoyer-Geindre ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Intracellular Calcium ◽  
Von Willebrand Factor ◽  
Small Gtpases ◽  
Dominant Negative ◽  
Calcium Handling ◽  
Regulated Secretion ◽  
Nos Inhibitors ◽  
Von Willebrand ◽  
Willebrand Factor

Regulated secretion of EC (endothelial cell) vWF (von Willebrand factor) is part of the haemostatic response. It occurs in response to secretagogues that raise intracellular calcium or cAMP. Statins are cholesterol-lowering drugs used for the treatment of cardiovascular disease. We studied the effect of fluvastatin on regulated secretion of vWF from HUVEC (human umbilical-vein ECs). Secretion in response to thrombin, a protease-activated receptor-1 agonist peptide, histamine, forskolin and adrenaline (epinephrine) was inhibited. This inhibition was reversed by mevalonate or geranylgeranyl pyrophosphate, and mimicked by a geranylgeranyl transferase inhibitor, demonstrating that the inhibitory mechanism includes inhibition of protein geranylgeranylation. To investigate this mechanism further, calcium handling and NO (nitric oxide) regulation were studied in fluvastatin-treated HUVEC. Intracellular calcium mobilization did not correlate with vWF secretion. Fluvastatin increased eNOS [endothelial NOS (NO synthase)] expression, but NOS inhibitors failed to reverse the effect of fluvastatin on vWF secretion. Exogenous NO did not inhibit thrombin-induced vWF secretion. Many small GTPases are geranylgeranylated and some are activated by secretagogues. We overexpressed DN (dominant negative) Rho GTPases, RhoA, Rac1 and Cdc42 (cell division cycle 42), in HUVEC. DNCdc42 conferred inhibition of thrombin- and forskolin-induced vWF secretion. We conclude that, via inhibition of protein geranylgeranylation, fluvastatin is a broadspectrum inhibitor of regulated vWF secretion. Geranylgeranylated small GTPases with functional roles in regulated secretion, such as Cdc42, are potential targets for the inhibitory activity of fluvastatin.

Sign in / Sign up

Export Citation Format

Share Document