|
|
Prepublished online as a Blood First Edition Paper on October 10, 2002; DOI 10.1182/blood-2002-07-2281.
Submitted July 29, 2002
Accepted September 25, 2002
Critical independent regions in the VWF propeptide and mature VWF that enable normal VWF storage
Sandra L Haberichter, Paula Jacobi, and Robert R Montgomery*
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA
Blood Research Institute, The Blood Center of Southeastern Wisconsin, Milwaukee, WI, USA
* Corresponding author; email: bob{at}bcsew.edu.
Von Willebrand factor (VWF) is synthesized in endothelial cells where it is stored in Weibel-Palade bodies. Administration of 1-desamino-8-D-arginine-vasopressin (DDAVP) to patients with type 1 von Willebrand disease and to normal individuals causes a rapid increase in plasma VWF levels. This increase is the result of stimulated release of VWF from Weibel-Palade bodies in certain beds of endothelial cells. The VWF propeptide (VWFpp) targets VWF to storage granules through a non-covalent association. The nature of the VWFpp/VWF interaction was investigated by utilizing cross-species differences in VWF storage. While the canine VWFpp trafficks to storage granules and facilitates the multimerization of human VWF, it does not direct human VWF to storage granules. Since storage takes place after furin cleavage, this defect appears to be due to the defective interaction of canine VWFpp and human VWF. To determine the regions within VWFpp and VWF important for this VWFpp/VWF association and co-storage, a series of human-canine chimeric VWFpp and propeptide-deleted VWF ( pro) constructs were produced and expressed in AtT-20 cells. The intracellular localization of co-expressed proteins was examined by confocal microscopy. Two amino acids, 416 in VWFpp and 869 in the mature VWF molecule, were identified as being critical for the association and granular storage of VWF.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
M. van den Biggelaar, A. B. Meijer, J. Voorberg, and K. Mertens
Intracellular cotrafficking of factor VIII and von Willebrand factor type 2N variants to storage organelles
Blood,
March 26, 2009;
113(13):
3102 - 3109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. A. Maroney, S. L. Haberichter, P. Friese, M. L. Collins, J. P. Ferrel, G. L. Dale, and A. E. Mast
Active tissue factor pathway inhibitor is expressed on the surface of coated platelets
Blood,
March 1, 2007;
109(5):
1931 - 1937.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Michaux, T. J. Pullen, S. L. Haberichter, and D. F. Cutler
P-selectin binds to the D'-D3 domains of von Willebrand factor in Weibel-Palade bodies
Blood,
May 15, 2006;
107(10):
3922 - 3924.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. L. Haberichter, E. P. Merricks, S. A. Fahs, P. A. Christopherson, T. C. Nichols, and R. R. Montgomery
Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells
Blood,
January 1, 2005;
105(1):
145 - 152.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. J. Lenting, E. Westein, V. Terraube, A.-S. Ribba, E. G. Huizinga, D. Meyer, P. G. de Groot, and C. V. Denis
An Experimental Model to Study the in Vivo Survival of von Willebrand Factor: BASIC ASPECTS AND APPLICATION TO THE R1205H MUTATION
J. Biol. Chem.,
March 26, 2004;
279(13):
12102 - 12109.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Padilla, J. L. Moake, A. Bernardo, C. Ball, Y. Wang, M. Arya, L. Nolasco, N. Turner, M. C. Berndt, B. Anvari, et al.
P-selectin anchors newly released ultralarge von Willebrand factor multimers to the endothelial cell surface
Blood,
March 15, 2004;
103(6):
2150 - 2156.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
