von Willebrand factor storage and multimerization: 2 independent intracellular processes.

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 (Deltapro) 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 Deltapro 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 Deltapro 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. (Blood. 2000;96:1808-1815)