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Hamostaseologie 2017; 37(01): 59-72
DOI: 10.5482/HAMO-16-06-0018
State of the art
Schattauer GmbH

Von Willebrand factor processing

Von-Willebrand-Faktor-Prozessierung
Maria A. Brehm
1   Pädiatrische Hämatologie und Onkologie, Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany
› Author Affiliations
Further Information

Publication History

received: 29 June 2016

accepted in revised form: 03 November 2016

Publication Date:
28 December 2017 (online)

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Summary

Von Willebrand factor (VWF) is a multimeric glycoprotein essential for primary haemostasis that is produced only in endothelial cells and megakaryocytes. Key to VWF’s function in recruitment of platelets to the site of vascular injury is its multimeric structure. The individual steps of VWF multimer biosynthesis rely on distinct posttranslational modifications at specific pH conditions, which are realized by spatial separation of the involved processes to different cell organelles. Production of multimers starts with translocation and modification of the VWF prepropolypeptide in the endoplasmic reticulum to produce dimers primed for glycosylation. In the Golgi apparatus they are further processed to multimers that carry more than 300 complex glycan structures functionalized by sialylation, sulfation and blood group determinants. Of special importance is the sequential formation of disulfide bonds with different functions in structural support of VWF multimers, which are packaged, stored and further processed after secretion. Here, all these processes are being reviewed in detail including background information on the occurring biochemical reactions.

Zusammenfassung

Der von-Willebrand-Faktor (VWF) spielt eine zentrale Rolle in der primären Hämostase. Grundvoraussetzung hierfür ist seine multimere Struktur, die die effiziente Rekrutierung von Thrombozyten an die verletzte Gefäßwand ermöglicht. Die einzelnen Schritte der VWF-Multimersynthese bestehen aus verschiedenen posttranslationalen Modifikationen, die nacheinander bei bestimmten pH-Bedingungen ablaufen müssen. Deshalb finden sie in unterschiedlichen Zellorganellen statt. Zunächst werden die VWF-Monomere im endoplasmatischen Retikulum zu Dimeren verknüpft und vorglykolisiert. Im Golgi-Apparat werden diese zu Multimeren zusammengefügt, die nach abgeschlossener Modifikation mehr als 300 komplexe Zuckerstrukturen tragen, welche durch Sialylierung, Sulfonierung und mit Blutgruppenantigenen funktionalisiert wurden. Von besonderer Wichtigkeit ist die sequenzielle Ausbildung von Disulfidbrücken, die verschiedene Aufgaben in der Strukturgebung der VWF-Multimere besitzen. Die Multimere werden spiralisiert, gelagert und nach Sekretion weiter modifiziert. Dieser Artikel liefert einen detaillierten Überblick über diese Prozesse, inklusive Grundlageninformationen zu den biochemischen Reaktionen.

Keywords

von Willebrand factor - multimer biosynthesis - disulfide bonds - glycosylation

Schlüsselwörter

von-Willebrand-Faktor - Disulfidbrücken - Glykosylierung - Multimersynthese
 

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