Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells. Blood 2005 Jan 01;105(1):145-52
Date
08/28/2004Pubmed ID
15331450Pubmed Central ID
PMC3938105DOI
10.1182/blood-2004-02-0464Scopus ID
2-s2.0-11144247649 (requires institutional sign-in at Scopus site) 60 CitationsAbstract
Type 3 von Willebrand disease (VWD) is a severe hemorrhagic defect in humans. We now identify the homozygous mutation in the Chapel Hill strain of canine type 3 VWD that results in premature termination of von Willebrand factor (VWF) protein synthesis. We cultured endothelium from VWD and normal dogs to study intracellular VWF trafficking and Weibel-Palade body formation. Weibel-Palade bodies could not be identified in the canine VWD aortic endothelial cells (VWD-AECs) by P-selectin, VWFpp, or VWF immunostaining and confocal microscopy. We demonstrate the reestablishment of Weibel-Palade bodies that recruit endogenous P-selectin by expressing wild-type VWF in VWD-AECs. Expression of mutant VWF proteins confirmed that VWF multimerization is not necessary for Weibel-Palade body creation. Although the VWF propeptide is required for the formation of Weibel-Palade bodies, it cannot independently induce the formation of the granule. These VWF-null endothelial cells provide a unique opportunity to examine the biogenesis of Weibel-Palade bodies in endothelium from a canine model of type 3 VWD.
Author List
Haberichter SL, Merricks EP, Fahs SA, Christopherson PA, Nichols TC, Montgomery RRMESH terms used to index this publication - Major topics in bold
Amino Acid SequenceAnimals
Aorta
Base Sequence
Cells, Cultured
Dogs
Endothelial Cells
Frameshift Mutation
Gene Expression Regulation
Humans
Molecular Sequence Data
Protein Processing, Post-Translational
Weibel-Palade Bodies
von Willebrand Diseases
von Willebrand Factor
