Von Willebrand factor storage and multimerization: 2 independent intracellular processes

被引:66
作者
Haberichter, SL
Fahs, SA
Montgomery, RR
机构
[1] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA
[2] Blood Ctr SE Wisconsin Inc, Blood Res Inst, Milwaukee, WI 53201 USA
[3] Childrens Hosp Wisconsin, Milwaukee, WI 53201 USA
关键词
D O I
10.1182/blood.V96.5.1808.h8001808_1808_1815
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The von Willebrand factor propeptide, vW AgII, has been shown to be required for the formation of VWF multimers and sorting of VWF to storage granules; whether these 2 processes are independent events has been unclear. Chimeric constructs of human and canine VWF were developed to further define these processes and to determine whether they are independent intracellular events. Cells expressing only mature vWF (Delta pro) produced vWF dimers that were not stored in AtT-20 cells; whereas the expression of vW AgII alone resulted in vW AgII granular storage. Expression of vW AgII in trans with Delta pro resulted in the multimerization of vWF and colocalized storage of vW AgII and vWF. Expression of canine vW AgII in trans or cis with human Delta pro resulted in the multimerization of human vWF, with no storage of human vWF but with normal storage of canine vW AgII. This dissociation of functions indicates that the signals for multimerization of vWF are differ-ent from the signals for trafficking of VWF to storage and demonstrates that vWF storage and multimerization are 2 independent intracellular processes. vW AgII contains the signal(s) required for trafficking to storage, and only through interaction with vW AgII is VWF chaperoned into granules. (C) 2000 by The American Society of Hematology.
引用
收藏
页码:1808 / 1815
页数:8
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