Faculty Collaboration Database

The von Willebrand factor propeptide (VWFpp) traffics an unrelated protein to storage. Arterioscler Thromb Vasc Biol 2002 Jun 01;22(6):921-6

Date

06/18/2002

Pubmed ID

12067899

DOI

10.1161/01.atv.0000017063.36768.87

Scopus ID

2-s2.0-0036075304 (requires institutional sign-in at Scopus site)   35 Citations

Abstract

The von Willebrand factor (VWF) propeptide (VWFpp) is critical for the targeting of VWF multimers to storage granules. VWFpp alone efficiently navigates the storage pathway in AtT-20 and endothelial cells and chaperones mature VWF multimers to storage granules when the two proteins are expressed in cis or in trans. To further define the role of VWFpp in granular sorting, we examined its ability to sort an unrelated protein, C3alpha into the regulated secretory pathway. Chimeric constructs of VWFpp and the alpha-chain of C3 were developed. The C3alpha protein expressed alone did not sort to granules in AtT-20 cells. The trans expression of C3alpha and VWFpp resulted in granular storage of VWFpp but no corresponding storage of C3alpha. When C3alpha is expressed as a single chain molecule with VWFpp that was rendered uncleavable by furin, C3alpha is re-routed to storage and is colocalized with VWFpp. The uncleavable protein was expressed in bovine aortic endothelial cells where it sorted to Weibel-Palade bodies, colocalized with bovine VWF, and was released when agonist stimulated. We now demonstrate that VWFpp re-routes a constitutively secreted protein to the regulated storage pathway. Furthermore, our studies suggest that the VWFpp storage signal is contained within amino acids 201 to 741.

Author List

Haberichter SL, Jozwiak MA, Rosenberg JB, Christopherson PA, Montgomery RR

Author

Robert R. Montgomery MD Adjunct Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Aorta
Cattle
Cell Line
Complement C3a
Endothelium, Vascular
Mice
Peptides
Protein Precursors
Protein Sorting Signals
Protein Transport
Proteins
Recombinant Fusion Proteins
Secretory Vesicles
Weibel-Palade Bodies
von Willebrand Factor