6. von Willebrand Factor

  • vWF synthesized in:
    • endothelial cells
    • megakaryocytes
  • Encoded in gene on Chr 12 (51 introns)
    Pro-vWF and Mature vWF
  • Multivalent adhesive protein
  • Function:
    • binds to subendothelial collagen and mediates platelet attachment at high shear
    • facilitates platelet aggregation and
    • 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