Biogenesis of Weibel–Palade bodies

Hannah, Matthew J.; Williams, Richard A.; Kaur, Jasber; Hewlett, Lindsay; Cutler, Daniel F.

doi:10.1016/s1084-9521(02)00061-7

Cited by 74 publications

(75 citation statements)

References 90 publications

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“…Further evidence that PAR2 produces less of an inflammatory effect in endothelial cells is derived from the observation that PAR2 leads to less vascular permeability changes than PAR1. 32,52 Weibel-Palade bodies also contain premature von Willebrand factor, interleukin-8, endothelin-1, ␣1,3 fucosyltransferase, CD63, 53,54 and possibly tissue plasminogen activator (t-PA). 40,55 Our findings raise the question of whether the other contents of WPBs also display differential signaling.…”

Section: Differential Par and Camp-dependent Exocytosis 2741mentioning

confidence: 99%

Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Cleator

Zhu

Vaughan

et al. 2006

Blood

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Thrombin-mediated endothelial-cell release of von Willebrand factor (VWF) and P-selectin functionally links proteaseactivated receptors (PARs) to thrombosis and inflammation. VWF release can be stimulated by both Ca 2؉ and cAMP, and, although both VWF and P-selectin are found in Weibel-Palade bodies (WPBs), we found that their release could be differentially regulated. In these studies, human umbilical vein endothelial cells stimulated with cAMP or PAR2-AP led to a delayed release of VWF and significantly less P-selectin release compared with histamine, thrombin, or PAR1-AP. Doseresponse studies revealed that PAR2-AP was significantly less efficacious in promoting the release of P-selectin compared with VWF. PAR2-AP-induced robust stimulation of intracellular Ca 2؉ coupled with a significantly greater inhibitory effect of calcium chelation on release of VWF compared with cell-surface expression of P-selectin, suggests an additional Ca 2؉ -independent pathway involved in release of P-selectin. PAR2-AP failed to increase global cAMP levels; however, inhibition of protein kinase A

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Section: Differential Par and Camp-dependent Exocytosis 2741mentioning

confidence: 99%

Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Cleator

Zhu

Vaughan

et al. 2006

Blood

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“…1 are large rod-shaped secretory granules found in endothelial cells (1)(2)(3)(4). Regulated exocytosis of WPBs delivers the adhesive protein von Willebrand factor (VWF) and the leukocyte adhesion molecule P-selectin to the endothelial cell surface, where they play important roles in vascular hemostasis and inflammation (1,5,6).…”

Section: Weibel-palade Bodies (Wpbs)mentioning

confidence: 99%

Differential Kinetics of Cell Surface Loss of von Willebrand Factor and Its Propolypeptide after Secretion from Weibel-Palade Bodies in Living Human Endothelial Cells

Hannah¹,

Skehel

Erent³

et al. 2005

Journal of Biological Chemistry

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“…A great deal is known about the complex biosynthesis of VWF, including its cleavage into a pro-peptide plus mature protein by furin, and the need for interactions between these two components for tubule formation to occur (reviewed in Hannah et al, 2002;Michaux and Cutler, 2004;van Mourik et al, 2002); however, even simple questions, such as exactly where along the secretory pathway the tubules start to drive the formation of this uniquely-shaped organelle, remain unanswered.…”

Section: Introductionmentioning

confidence: 99%

High-pressure freezing provides insights into Weibel-Palade body biogenesis

Zenner

Collinson

Michaux

et al. 2007

Journal of Cell Science

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The Weibel-Palade bodies (WPBs) of endothelial cells play an important role in haemostasis and the initiation of inflammation, yet their biogenesis is poorly understood. Tubulation of their major content protein, von Willebrand factor (VWF), is crucial to WPB function, and so we investigated further the relationship between VWF tubule formation and WPB formation in human umbilical vein endothelial cells (HUVECs). By using high-pressure freezing and freeze substitution before electron microscopy, we visualised VWF tubules in the trans-Golgi network (TGN), as well as VWF subunits in vesicular structures. Tubules were also seen in WPBs that were connected to the TGN by membranous stalks. Tubules are disorganised in the immature WPBs but during maturation we found a dramatic increase in the spatial organisation of the tubules and in organelle electron density. We also found coated budding profiles suggestive of the removal of missorted material after initial formation of these granules. Finally, we discovered that these large, seemingly rigid, organelles flex at hinge points and that the VWF tubules are interrupted at these hinges, facilitating organelle movement around the cell. The use of high-pressure freezing was vital in this study and it suggests that this technique might prove essential to any detailed characterisation of organelle biogenesis.

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Biogenesis of Weibel–Palade bodies

Cited by 74 publications

References 90 publications

Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Differential regulation of endothelial exocytosis of P-selectin and von Willebrand factor by protease-activated receptors and cAMP

Differential Kinetics of Cell Surface Loss of von Willebrand Factor and Its Propolypeptide after Secretion from Weibel-Palade Bodies in Living Human Endothelial Cells

High-pressure freezing provides insights into Weibel-Palade body biogenesis

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