Requirement for both D domains of the propolypeptide in von Willebrand factor multimerization and storage.

Abstract:

: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 rod-shaped 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 multimerization 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 multimerization and storage.

journal_name

Thromb Haemost

authors

Journet AM,Saffaripour S,Wagner DD

subject

Has Abstract

pub_date

1993-12-20 00:00:00

pages

1053-7

issue

6

eissn

0340-6245

issn

2567-689X

journal_volume

70

pub_type

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