Case Study#5   1  2  3  4  5  6  7  8  9  10  11  12  13  14  15  16   von Willebrand Factor vWF synthesized in: endothelial cells megakaryocytes Encoded in gene on Chr 12 (51 introns) Multivalent adhesive protein Function: binds to subendothelial collagen and mediates platelet attachment at high shear facilitates platelet aggregation and spreading stabilizes Factor VIII in circulation prevents degradation/inhibition Synthesis of vWF in EC Pro-vWF enters ER N-linked glycosylation occurs monomers form dimers by disulfide bonds of cysteine residues monomers do not progress Dimers enter Golgi O-linked glycosylation and sulfation (increase MW) some multimers formed in late Golgi (all multimers made from dimers) Storage in Weibel-Palade bodies cleaved by protease to mature vWF many multimers made some multimers still contain pro-vWF