Requirement for Both D Domains of the Propolypeptide in von Willebrand Factor Muitimerization and Storage

Agnès M Journet; Simin Saffaripour; Denisa D Wagner

doi:10.1055/s-0038-1649724

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1993; 70(06): 1053-1057
DOI: 10.1055/s-0038-1649724

Original Article

Von Willebrand Factor and Endothelial Cells

Schattauer GmbH Stuttgart

Requirement for Both D Domains of the Propolypeptide in von Willebrand Factor Muitimerization and Storage

Agnès M Journet

¹Centre d'Etudes Nucléaires de Grenoble, Unité INSERM, U238, DBMS/ICH, Grenoble, France

,

Simin Saffaripour

²The Center for Hemostasis and Thrombosis Research, Division of Hematology/Oncology, New England Medical Center and Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA, USA

,

Denisa D Wagner

²The Center for Hemostasis and Thrombosis Research, Division of Hematology/Oncology, New England Medical Center and Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA, USA

› Author Affiliations

Abstract

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Summary

Biosynthesis of the adhesive glycoprotein von Willebrand factor (vWf) by endothelial cells results in constitutive secretion of small multimers and storage of the largest multimers in rodshaped granules called Weibel-Palade bodies. This pattern is reproduced by expression of pro-vWf in heterologous cells with a regulated pathway of secretion, that store the recombinant protein in similar elongated granules. In these cells, deletion of the vWf prosequence prevents vWf storage. The prosequence, composed of two homologous domains (D1 and D2), actively participates in vWf multimer formation as well. We expressed deletion mutants lacking either the D1 domain (D2vWf) or the D2 domain (D1vWf) in various cell lines to analyze the relative importance of each domain in vWf muitimerization and storage. Both proteins were secreted efficiently without being retained in the endoplasmic reticulum. Despite this, neither multimerized past the dimer stage and they were not stored. We conclude that several segments of the prosequence are jointly involved in vWf muitimerization and storage.

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References

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