von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends.

@article{Lenting2015vonWF,
  title={von Willebrand factor biosynthesis, secretion, and clearance: connecting the far ends.},
  author={Peter J. Lenting and Olivier D. Christophe and C{\'e}cile V. Denis},
  journal={Blood},
  year={2015},
  volume={125 13},
  pages={
          2019-28
        }
}
To understand the placement of a certain protein in a physiological system and the pathogenesis of related disorders, it is not only of interest to determine its function but also important to describe the sequential steps in its life cycle, from synthesis to secretion and ultimately its clearance. von Willebrand factor (VWF) is a particularly intriguing case in this regard because of its important auxiliary roles (both intra- and extracellular) that implicate a wide range of other proteins… Expand
Targeting von Willebrand Factor-Mediated Inflammation.
TLDR
Findings support the hypothesis that VWF is involved in regulating inflammation and suggest that novel VWF-targeted therapies may be useful inhibitors of this critical step in inflammatory pathogenesis. Expand
Von Willebrand factor processing.
  • M. Brehm
  • Chemistry, Medicine
  • Hamostaseologie
  • 2017
TLDR
The individual steps of VWF multimer biosynthesis rely on distinct posttranslational modifications at specific pH conditions, which are realized by spatial separation of the involved processes to different cell organelles, including background information on the occurring biochemical reactions. Expand
von Willebrand factor and inflammation
TLDR
A more direct link between VWF and inflammation has become apparent with the discovery that VWF is able to recruitLeukocytes, either via direct leukocyte binding or by recruiting platelets which in turn will attract leukocytes. Expand
Von Willebrand Factor in Health and Disease
Abstract— Von Willebrand factor (vWF), the key component of hemostasis, is synthesized in endothelial cells and megakaryocytes and released into the blood as high molecular weight multimericExpand
Von Willebrand factor: structure, properties and role in the process of hemostasis
The article reviews the scientific papars on the structure, function and biological role of von Willebrand factor (vWF). The vWF mainly was considered as the main factor in the development ofExpand
von Willebrand factor clearance – biological mechanisms and clinical significance
TLDR
Improved understanding regarding VWF clearance is not only of direct biological relevance, but may also have important implications for the development of novel therapeutic agents with extended plasma half‐lives for the treatment of both VWD and haemophilia A. Expand
Functional Roles of the von Willebrand Factor Propeptide.
TLDR
The large size and several biologically interesting structural features suggest that there may be roles that the VWFpp plays in hemostasis or associated physiological processes such as angiogenesis or wound repair. Expand
The Biological Significance of von Willebrand Factor O-Linked Glycosylation.
TLDR
Von Willebrand factor O-linked glycans have been shown to modulate tertiary protein structure, susceptibility to ADAMTS13 proteolysis, platelet tethering, and VWF circulatory half-life. Expand
Physiological Roles of the von Willebrand Factor-Factor VIII Interaction.
TLDR
The role of the VWF-FVIII interaction in vascular physiology is provided, which is an acute phase protein that has multiple roles in vascular inflammation and is massively secreted from Weibel-Palade bodies upon endothelial cell activation. Expand
Industrial production of clotting factors: Challenges of expression, and choice of host cells
TLDR
The nature of the expression challenges for the industrial production of recombinant forms of blood coagulation factors, vis‐à‐vis the translational and post‐translational bottlenecks, as well as the choice of host cell lines for high‐fidelity production are reviewed. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 107 REFERENCES
Clearance of von Willebrand factor.
TLDR
An overview of recent findings with regard to the molecular basis of von Willebrand factor clearance is provided and recent data describing chemically modification of VWF as an approach to prolong the half-life of the VWF/FVIII complex are discussed. Expand
von Willebrand factor: the old, the new and the unknown
TLDR
An overview of advances concerning the various structural and functional aspects of VWF will be provided, and it has become increasingly clear that VWF is a more all‐round protein than originally thought, given its involvement in several pathologic processes beyond hemostasis. Expand
5 Molecular cloning, expression and assembly of multimeric von Willebrand factor*
TLDR
In particular, the construction of point and deletion mutants of vWF, employing vWF cDNA, and subsequent expression in heterologous cells have demonstrated that proteolytic processing of pro-vWF, between arginine and serine, to generate free propolypeptide and mature vWF is not required for multimerization. Expand
On the Versatility of von Willebrand Factor
TLDR
It is become aware that VWF has a more versatile character than previously thought, given its potential role in various non-hemostatic processes, like intimal thickening, tumor cell apoptosis and inflammatory processes. Expand
Molecular cloning, expression and assembly of multimeric von Willebrand factor.
TLDR
In particular, the construction of point and deletion mutants of vWF, employing vWF cDNA, and subsequent expression in heterologous cells have demonstrated that proteolytic processing of pro-vWF, between arginine and serine, to generate free propolypeptide and mature vWF is not required for multimerization. Expand
The secretion of von Willebrand factor from endothelial cells; an increasingly complicated story
TLDR
This review aims to provide a snapshot of the current understanding of those components, in particular the members of the Rab family, acting in the increasingly complex story of VWF secretion. Expand
Sulfation of von Willebrand factor.
TLDR
Sodium chlorate, an inhibitor of adenosine triphosphate-sulfurylase, blocks sulfation of vWF without affecting either the ability to assemble into high molecular weight multimers or the ability of vWA multimers to enter Weible-Palade bodies. Expand
Biochemistry and genetics of von Willebrand factor.
  • J. Sadler
  • Chemistry, Medicine
  • Annual review of biochemistry
  • 1998
TLDR
Growing body of information about VWF synthesis, structure, and function has allowed the reclassification of VWD based upon distinct pathophysiologic mechanisms that appear to correlate with clinical symptoms and the response to therapy. Expand
Intracellular Storage and Regulated Secretion of Von Willebrand Factor in Quantitative Von Willebrand Disease*
TLDR
Immunofluorescence and electron microscopy data showed that the pseudo-WPBs formed by missense mutant C1060Y are indistinguishable from those formed by normal VWF, suggesting defects in the intracellular storage and regulated secretion of VWF following ER retention may be a common mechanism underlying VWD with a quantitative deficiency of VWf. Expand
The plasma von Willebrand factor O‐glycome comprises a surprising variety of structures including ABH antigens and disialosyl motifs
TLDR
An exhaustive profile of the human plasma‐derived VWF O‐glycan structures is provided to help the understanding of their role in VWF regulation and properties and to facilitate research aimed at providing a better understanding of the influence of glycosylation on VWF functions. Expand
...
1
2
3
4
5
...