title: Mutations in the D1 domain of von Willebrand factor impair their propeptide-dependent multimerization, intracellular trafficking and secretion.
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.
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. yjjessie@163.com.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. windfr@163.com.
authors.forename: Zhenni
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. szjs2001@yahoo.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Su
authors.affiliation: Department of Surgery, National University of Singapore; Cardiovascular Research Institute (CVRI), National University Heart Centre Singapore (NUHCS), National University Health System, Singapore, 999002, Singapore. surwang@nus.edu.sg.
authors.forename: Jiong-Wei
authors.initials: JW
authors.lastname: Wang
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. jenna20110507@gmail.com.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, 215003, China. koala_a@126.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Ling
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. baixia@suda.edu.cn.
authors.forename: Xia
authors.initials: X
authors.lastname: Bai
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. 13305275503@163.com.
authors.forename: Wanyan
authors.initials: W
authors.lastname: Ouyang
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. zwang11@sina.com.
authors.forename: Zhaoyue
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. 109334862@qq.com.
authors.forename: Ziqiang
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Collaborative Innovation Center of Hematology, MOH Key Lab of Thrombosis and Hemostasis, Jiangsu Institute of Hematology, the First Affiliated Hospital, Soochow University, Suzhou, 215006, China. cshcma@medmail.com.cn.
authors.forename: Changgeng
authors.initials: C
authors.lastname: Ruan
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D009154:Mutation; D014162:Transfection; D014841:von Willebrand Factor / Q000235:genetics*
chemical_list: D014841:von Willebrand Factor