|
|
Blood, 15 August 2008, Vol. 112, No. 4, pp. 957-964.
Prepublished online as a Blood First Edition Paper on March 14, 2008; DOI 10.1182/blood-2007-12-130740.
 Previous Article | Next Article 
Submitted December 21, 2007
Accepted March 10, 2008
Basal secretion of von Willebrand factor from human endothelial cells
Jonathan P Giblin, Lindsay J Hewlett, and Matthew J Hannah*
Department of Molecular Neuroendocrinology, Medical Research Council National Institute for Medical Research, London, United Kingdom
* Corresponding author; email: mhannah{at}nimr.mrc.ac.uk.
Endothelial cells store the adhesive glycoprotein von Willebrand factor (VWF) in Weibel-Palade Bodies (WPBs), distinctively shaped regulated secretory organelles that undergo exocytosis in response to secretagogue. A significant proportion of newly synthesised VWF is also secreted spontaneously from non-stimulated cells, through what is thought to be the constitutive secretory pathway. To learn more about VWF trafficking we performed kinetic analyses of the storage and non-stimulated secretion of VWF in cultured human endothelial cells. We found that the majority of VWF was secreted through a route that was significantly delayed compared to constitutive secretion, although this pathway was responsible for secretion of a small amount of un-cleaved VWF precursor. Disruption of pH-dependent sorting processes with ammonium chloride converted the secretion kinetics of mature VWF to that of its precursor. Conversely, preventing constitutive secretion of nascent protein with brefeldin A had only a modest effect on the spontaneous release of VWF demonstrating that the majority of VWF secreted by non-stimulated cells was not constitutive secretion but basal release of a post-Golgi storage organelle, presumably the WPB. These data suggest that VWF is sorted to the regulated secretory pathway in endothelial cells much more efficiently than previously reported.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
Related Article in Blood Online:
-
VWF secretion: what's in a name?
- Jill Johnsen and José A. López
Blood 2008 112: 926-927.
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
S. F. De Meyer, H. Deckmyn, and K. Vanhoorelbeke
von Willebrand factor to the rescue
Blood,
May 21, 2009;
113(21):
5049 - 5057.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
V. Babich, L. Knipe, L. Hewlett, A. Meli, J. Dempster, M. J. Hannah, and T. Carter
Differential Effect of Extracellular Acidosis on the Release and Dispersal of Soluble and Membrane Proteins Secreted from the Weibel-Palade Body
J. Biol. Chem.,
May 1, 2009;
284(18):
12459 - 12468.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. van den Biggelaar, E. A.M. Bouwens, N. A. Kootstra, R. P. Hebbel, J. Voorberg, and K. Mertens
Storage and regulated secretion of factor VIII in blood outgrowth endothelial cells
Haematologica,
May 1, 2009;
94(5):
670 - 678.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Huang, R. Roth, J. E. Heuser, and J. E. Sadler
Integrin {alpha}v{beta}3 on human endothelial cells binds von Willebrand factor strings under fluid shear stress
Blood,
February 12, 2009;
113(7):
1589 - 1597.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. W.Y. Lui-Roberts, F. Ferraro, T. D. Nightingale, and D. F. Cutler
Aftiphilin and {gamma}-Synergin Are Required for Secretagogue Sensitivity of Weibel-Palade Bodies in Endothelial Cells
Mol. Biol. Cell,
December 1, 2008;
19(12):
5072 - 5081.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
