Von Willebrand factor storage and multimerization: 2 independent intracellular processes

The von Willebrand factor propeptide, vW AgII, has been shown to be require d for the formation of VWF multimers and sorting of VWF to storage granules ; whether these 2 processes are independent events has been unclear. Chimer ic constructs of human and canine VWF were developed to further define thes e processes and to determine whether they are independent intracellular eve nts. 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 re sulted in vW AgII granular storage. Expression of vW AgII in trans with Del ta 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 Delt a pro resulted in the multimerization of human vWF, with no storage of huma n vWF but with normal storage of canine vW AgII. This dissociation of funct ions indicates that the signals for multimerization of vWF are differ-ent f rom 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 t hrough interaction with vW AgII is VWF chaperoned into granules. (C) 2000 b y The American Society of Hematology.