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… 

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References

SHOWING 1-10 OF 102 REFERENCES

von Willebrand factor: the old, the new and the unknown

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.

On the Versatility of von Willebrand Factor

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.

Clearance of von Willebrand factor

A better insight into the complex clearance pathways of VWF may help to better understand the clinical implications of aberrant clearance in the pathogenesis of von Willebrand disease and perhaps other disorders as well as aid in developing alternative therapeutic approaches.

Molecular cloning, expression and assembly of multimeric von Willebrand factor.

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.

The secretion of von Willebrand factor from endothelial cells; an increasingly complicated story

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.

Biochemistry and genetics of von Willebrand factor.

  • J. Sadler
  • Biology, Medicine
    Annual review of biochemistry
  • 1998
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.

Sulfation of von Willebrand factor.

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.

Intracellular Storage and Regulated Secretion of Von Willebrand Factor in Quantitative Von Willebrand Disease*

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.

The plasma von Willebrand factor O‐glycome comprises a surprising variety of structures including ABH antigens and disialosyl motifs

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.
...