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Local elongation of endothelial cell-anchored von Willebrand factor strings precedes ADAMTS13 protein-mediated proteolysis

(2011) JOURNAL OF BIOLOGICAL CHEMISTRY. 286(42). p.36361-36367
Author
Organization
Abstract
Platelet-decorated von Willebrand factor (VWF) strings anchored to the endothelial surface are rapidly cleaved by ADAMTS13. Individual VWF string characteristics such as number, location, and auxiliary features of the ADAMTS13 cleavage sites were explored here using imaging and computing software. By following changes in VWF string length, we demonstrated that VWF strings are cleaved multiple times, successively shortening string length in the function of time and generating fragments ranging in size from 5 to over 100 mu m. These are larger than generally observed in normal plasma, indicating that further proteolysis takes place in circulation. Interestingly, in 89% of all cleavage events, VWF strings elongate precisely at the cleavage site before ADAMTS13 proteolysis. These local elongations are a general characteristic of VWF strings, independent of the presence of ADAMTS13. Furthermore, large elongations, ranging in size from 1.4 to 40 mu m, occur at different sites in space and time. In conclusion, ADAMTS13-mediated proteolysis of VWF strings under flow is preceded by large elongations of the string at the cleavage site. These elongations may lead to the simultaneous exposure of many exosites, thereby facilitating ADAMTS13-mediated cleavage.
Keywords
THROMBOTIC THROMBOCYTOPENIC PURPURA, VONWILLEBRAND-FACTOR MULTIMERS, WEIBEL-PALADE BODIES, FLUID SHEAR-STRESS, SELF-ASSOCIATION, FACTOR-VIII, P-SELECTIN, ULTRALARGE, CLEAVAGE, FLOW

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Chicago
De Ceunynck, Karen, Susana Rocha, Hendrik Feys, Simon F De Meyer, Hiroshi Uji-i, Hans Deckmyn, Johan Hofkens, and Karen Vanhoorelbeke. 2011. “Local Elongation of Endothelial Cell-anchored Von Willebrand Factor Strings Precedes ADAMTS13 Protein-mediated Proteolysis.” Journal of Biological Chemistry 286 (42): 36361–36367.
APA
De Ceunynck, Karen, Rocha, S., Feys, H., De Meyer, S. F., Uji-i, H., Deckmyn, H., Hofkens, J., et al. (2011). Local elongation of endothelial cell-anchored von Willebrand factor strings precedes ADAMTS13 protein-mediated proteolysis. JOURNAL OF BIOLOGICAL CHEMISTRY, 286(42), 36361–36367.
Vancouver
1.
De Ceunynck K, Rocha S, Feys H, De Meyer SF, Uji-i H, Deckmyn H, et al. Local elongation of endothelial cell-anchored von Willebrand factor strings precedes ADAMTS13 protein-mediated proteolysis. JOURNAL OF BIOLOGICAL CHEMISTRY. 2011;286(42):36361–7.
MLA
De Ceunynck, Karen, Susana Rocha, Hendrik Feys, et al. “Local Elongation of Endothelial Cell-anchored Von Willebrand Factor Strings Precedes ADAMTS13 Protein-mediated Proteolysis.” JOURNAL OF BIOLOGICAL CHEMISTRY 286.42 (2011): 36361–36367. Print.
@article{8549097,
  abstract     = {Platelet-decorated von Willebrand factor (VWF) strings anchored to the endothelial surface are rapidly cleaved by ADAMTS13. Individual VWF string characteristics such as number, location, and auxiliary features of the ADAMTS13 cleavage sites were explored here using imaging and computing software. By following changes in VWF string length, we demonstrated that VWF strings are cleaved multiple times, successively shortening string length in the function of time and generating fragments ranging in size from 5 to over 100 mu m. These are larger than generally observed in normal plasma, indicating that further proteolysis takes place in circulation. Interestingly, in 89\% of all cleavage events, VWF strings elongate precisely at the cleavage site before ADAMTS13 proteolysis. These local elongations are a general characteristic of VWF strings, independent of the presence of ADAMTS13. Furthermore, large elongations, ranging in size from 1.4 to 40 mu m, occur at different sites in space and time. In conclusion, ADAMTS13-mediated proteolysis of VWF strings under flow is preceded by large elongations of the string at the cleavage site. These elongations may lead to the simultaneous exposure of many exosites, thereby facilitating ADAMTS13-mediated cleavage.},
  author       = {De Ceunynck, Karen and Rocha, Susana and Feys, Hendrik and De Meyer, Simon F and Uji-i, Hiroshi and Deckmyn, Hans and Hofkens, Johan and Vanhoorelbeke, Karen},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  language     = {eng},
  number       = {42},
  pages        = {36361--36367},
  title        = {Local elongation of endothelial cell-anchored von Willebrand factor strings precedes ADAMTS13 protein-mediated proteolysis},
  url          = {http://dx.doi.org/10.1074/jbc.M111.271890},
  volume       = {286},
  year         = {2011},
}

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