Mutations in the D1 domain of von Willebrand factor impair their propeptide-dependent multimerization, intracellular trafficking and secretionReport as inadecuate




Mutations in the D1 domain of von Willebrand factor impair their propeptide-dependent multimerization, intracellular trafficking and secretion - Download this document for free, or read online. Document in PDF available to download.

Journal of Hematology and Oncology

, 8:73

First Online: 20 June 2015Received: 17 May 2015Accepted: 03 June 2015DOI: 10.1186-s13045-015-0166-9

Cite this article as: Yin, J., Ma, Z., Su, J. et al. J Hematol Oncol 2015 8: 73. doi:10.1186-s13045-015-0166-9

Abstract

We identified three novel mutations p.Gly39Arg, p.Lys157Glu, p.Cys379Gly and one previously known mutation p.Asp141Asn in the von Willebrand factor propeptide from three von Willebrand disease patients. All four mutations impaired multimerization of von Willebrand factor, due to reduced oxidoreductase activity of isomeric propeptide. These mutations resulted in the endothelial reticulum retention and impaired basal and stimulated secretions of von Willebrand factor. Our results support that the mutations in the D1 domain lead to defective multimerization, intracellular trafficking, and secretion of von Willebrand factor and result in bleeding of patients.

Keywordsvon Willebrand disease VWF propeptide VWF gene mutation VWF multimerization ER retention AbbreviationsVWDvon Willebrand disease

VWFvon Willebrand factor

ERendoplasmic reticulum

VWFppVWF propeptide

P1proband 1

P2proband 2

P3proband 3

NPnormal plasma

WTwild type

PMAPhorbol 12-myristate-13-acetate

Electronic supplementary materialThe online version of this article doi:10.1186-s13045-015-0166-9 contains supplementary material, which is available to authorized users.

Download fulltext PDF



Author: Jie Yin - Zhenni Ma - Jian Su - Jiong-Wei Wang - Xiaojuan Zhao - Jing Ling - Xia Bai - Wanyan Ouyang - Zhaoyue Wang - Ziq

Source: https://link.springer.com/



DOWNLOAD PDF




Related documents