PMID- 8204880
OWN - NLM
STAT- MEDLINE
DCOM- 19940712
LR  - 20210216
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 83
IP  - 12
DP  - 1994 Jun 15
TI  - von Willebrand factor proteolytic processing and multimerization precede the 
      formation of Weibel-Palade bodies.
PG  - 3536-44
AB  - 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.
FAU - Vischer, U M
AU  - Vischer UM
AD  - Center for Hemostasis and Thrombosis Research, New England Medical Center, 
      Boston, MA 02111.
FAU - Wagner, D D
AU  - Wagner DD
LA  - eng
GR  - R01 HL41002/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (Protein Precursors)
RN  - 0 (Sulfates)
RN  - 0 (von Willebrand Factor)
RN  - 0 (von Willebrand factor propolypeptide)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cells, Cultured
MH  - Cytoplasmic Granules/metabolism
MH  - Endothelium, Vascular/*metabolism/ultrastructure
MH  - Golgi Apparatus/metabolism
MH  - Humans
MH  - Hydrogen-Ion Concentration
MH  - Molecular Sequence Data
MH  - Protein Precursors/*metabolism
MH  - Sulfates/metabolism
MH  - Wound Healing
MH  - von Willebrand Factor/*metabolism
EDAT- 1994/06/15 00:00
MHDA- 1994/06/15 00:01
CRDT- 1994/06/15 00:00
PHST- 1994/06/15 00:00 [pubmed]
PHST- 1994/06/15 00:01 [medline]
PHST- 1994/06/15 00:00 [entrez]
AID - S0006-4971(20)78850-6 [pii]
PST - ppublish
SO  - Blood. 1994 Jun 15;83(12):3536-44.