Related Experiment Videos
von Willebrand factor and the endothelium
1Center of Hemostasis and Thrombosis Research, New England Medical Center, Boston, Massachusetts.
Mayo Clinic Proceedings
|June 1, 1991
Summary
Von Willebrand factor (vWF) requires specific intracellular processing for its active form. Proper dimerization, N-linked glycosylation, and multimerization in acidic conditions are crucial for vWF storage and release.
Area of Science:
- Biochemistry
- Cell Biology
- Hematology
Background:
- Endothelial cells produce von Willebrand factor (vWF), essential for hemostasis.
- vWF must undergo complex intracellular processing to achieve its biologically active multimeric form.
Purpose of the Study:
- To elucidate the intracellular processing steps required for von Willebrand factor (vWF) multimerization and secretion.
- To identify key molecular and environmental factors influencing vWF maturation.
Main Methods:
- Investigated the role of pro-vWF dimerization in the endoplasmic reticulum.
- Examined the necessity of N-linked glycosylation for vWF transport.
- Analyzed the impact of acidic pH and propolypeptide on vWF multimerization in the Golgi apparatus.
Main Results:
- Pro-vWF dimerization is essential for ER-to-Golgi transport; truncated subunits bypass this requirement.
- N-linked glycosylation is mandatory for vWF exit from the endoplasmic reticulum.
- Acidic pH and the propolypeptide are necessary for interchain disulfide bond formation and vWF multimerization.
Conclusions:
- vWF maturation involves sequential steps including dimerization, glycosylation, and pH-dependent multimerization.
- These processes ensure the formation of large, biologically active vWF multimers stored in Weibel-Palade bodies for release upon vascular injury.