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Blood, 1 September 2000, Vol. 96, No. 5, pp. 1808-1815
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Von Willebrand factor storage and multimerization: 2 independent
intracellular processes
Sandra L. Haberichter,
Scot
A. Fahs, and
Robert R. Montgomery
From the Blood Research Institute, The Blood Center of
Southeastern Wisconsin; the Department of Pediatrics, Medical College
of Wisconsin; Children's Hospital of Wisconsin, Milwaukee, WI.
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 ( 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 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 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 different 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.

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