Intracellular trafficking of factor VIII to von Willebrand factor storage granules.

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 ...

Intracellular co-trafficking of factor VIII and von Willebrand factor type 2N variants to storage organelles Running head: FVIII and VWF type 2N co-trafficking

Intracellular interaction of von Willebrand factor and factor VIII depends on cellular context: lessons from platelet-expressed factor VIII.

We have previously reported that ectopically expressed factor VIII (FVIII) is stored within platelets and is released upon platelet activation. Studies by others in various cell lines have suggested that having von Willebrand factor (VWF) coexpression is necessary for FVIII granular storage and for its secretion. We tested the importance of VWF coexpression for ectopic storage of FVIII in plate...

Factor VIII/V C-domain swaps reveal discrete C-domain roles in factor VIII function and intracellular trafficking

Factor VIII C-domains are believed to have specific functions in cofactor activity and in interactions with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor ...

Intracellular cotrafficking of factor VIII and von Willebrand factor type 2N variants to storage organelles.

Weibel-Palade bodies (WPBs) are the endothelial storage organelles that are formed upon von Willebrand factor (VWF) expression. Apart from VWF, WPBs contain a variety of hemostatic and inflammatory proteins. Some of these are thought to be targeted to WPBs by directly interacting with VWF in the secretory pathway. Previous studies have demonstrated that coexpression of factor VIII (FVIII) with ...