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von Willebrand factor proteolytic processing and multimerization precede
the formation of Weibel-Palade bodies
UM Vischer and DD Wagner
Center for Hemostasis and Thrombosis Research, New England Medical Center,
Boston, MA 02111.
We investigated the intracellular site of pro-von Willebrand factor
(pro-vWF) cleavage and multimerization, as well as the fate of the
propolypeptide (von Willebrand antigen II) after cleavage. Analysis of
subcellular fractions of endothelial cells metabolically labeled with
sulfate showed that both cleavage and covalent multimerization occur after
sulfation and precede the formation of Weibel-Palade bodies. Because
sulfation is a processing step localized to the trans-Golgi network (TGN),
our results indicate that multimerization and prosequence cleavage also
occur in this organelle. After cleavage, the propolypeptide remains
noncovalently associated with the mature vWF subunit. This association is
promoted by a high calcium concentration and an acidic pH (conditions
thought to prevail in the TGN) and explains the 1:1 stoichiometry of the
propolypeptide and mature vWF found in Weibel-Palade bodies. The
propolypeptide remains an integral part of the large multimeric vWF
aggregates in the Weibel-Palade body until secretion. When secretion occurs
under slightly acidic conditions, such as may be found in poorly perfused
wounds, the propolypeptide remains associated with the endothelial
surface-bound vWF, and may thus participate in the wound healing process.
Volume 83,
Issue 12,
pp. 3536-3544,
06/15/1994
Copyright © 1994 by The American Society of Hematology
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