Platelet Density-Dependent Partition of Platelet- von Willebrand Factor Between Alpha Granule and Non-Alpha Granule Pools

1987 ◽  
Vol 58 (03) ◽  
pp. 911-914 ◽  
Author(s):  
R I Parker ◽  
Brenda C Shafer ◽  
H R Gralnick
Keyword(s):  
Plasma Membrane ◽  
Von Willebrand Factor ◽  
Plasma Proteins ◽  
Buoyant Density ◽  
Membrane Permeabilization ◽  
Density Profiles ◽  
Density Dependent ◽  
Plasma Membrane Permeabilization ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryIn this study, we demonstrate that platelets contain a small hut significant amount of platelet-von Willebrand factor(vWf) not associated with α-granules. When platelets free of plasma proteins are exposed to micromolar concentrations ofdigitonin, plasma membrane permeabilization occurs without disruption of platelet granules. Employing this technique, wehave found that upon exposure of a total platelet population to 8 μM digitonin, 5% of total platelet-vWf is released into the supernatant; this occurs without release of (β-TG from α-granules. When platelets of discrete buoyant density profiles are tested, this extragranular platelet-vWf increased with decreasing platelet density. These findings suggest that a redistribution of platelet-vWf from α-granule to non-granule sites occurs coincident with a decrease inplatelet buoyant density.

scholarly journals Extensive contacts between ADAMTS13 exosites and von Willebrand factor domain A2 contribute to substrate specificity

Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1713-1719 ◽  
Author(s):  
Weiqiang Gao ◽  
Patricia J. Anderson ◽  
J. Evan Sadler
Keyword(s):  
Von Willebrand Factor ◽  
Plasma Proteins ◽  
Scissile Bond ◽  
Substrate Cleavage ◽  
Α Helix ◽  
Substrate Binding Sites ◽  
Von Willebrand ◽  
A2 Domain ◽  
Willebrand Factor ◽  
Specific Distance

Abstract The metalloprotease ADAMTS13 efficiently cleaves only the Tyr1605-Met1606 bond in the central A2 domain of multimeric von Willebrand factor (VWF), even though VWF constitutes only 0.02% of plasma proteins. This remarkable specificity depends in part on binding of the noncatalytic ADAMTS13 spacer domain to the C-terminal α-helix of VWF domain A2. By kinetic analysis of recombinant ADAMTS13 constructs, we show that the first thrombospondin-1, Cys-rich, and spacer domains of ADAMTS13 interact with segments of VWF domain A2 between Gln1624 and Arg1668, and together these exosite interactions increase the rate of substrate cleavage by at least approximately 300-fold. Internal deletion of Gln1624-Arg1641 minimally affected the rate of cleavage, indicating that ADAMTS13 does not require a specific distance between the scissile bond and auxiliary substrate binding sites. Smaller deletions of the P2-P9 or the P4′-P18′ residues on either side of the Tyr1605-Met1606 bond abolished cleavage, indicating that the metalloprotease domain interacts with additional residues flanking the cleavage site. Thus, specific recognition of VWF depends on cooperative, modular contacts between several ADAMTS13 domains and discrete segments of VWF domain A2.

scholarly journals Emerging Microfluidic Approaches for Platelet Mechanobiology and Interplay With Circulatory Systems

2021 ◽  
Vol 8 ◽  
Author(s):  
Yingqi Zhang ◽  
Savindi De Zoysa Ramasundara ◽  
Renee Ellen Preketes-tardiani ◽  
Vivian Cheng ◽  
Hongxu Lu ◽  
...  
Keyword(s):  
Blood Flow ◽  
Von Willebrand Factor ◽  
Plasma Proteins ◽  
Circulatory System ◽  
Microfluidic Platforms ◽  
Hemodynamic Forces ◽  
Vessel Walls ◽  
Sense And Respond ◽  
Von Willebrand ◽  
Willebrand Factor

Understanding how platelets can sense and respond to hemodynamic forces in disturbed blood flow and complexed vasculature is crucial to the development of more effective and safer antithrombotic therapeutics. By incorporating diverse structural and functional designs, microfluidic technologies have emerged to mimic microvascular anatomies and hemodynamic microenvironments, which open the floodgates for fascinating platelet mechanobiology investigations. The latest endothelialized microfluidics can even recapitulate the crosstalk between platelets and the circulatory system, including the vessel walls and plasma proteins such as von Willebrand factor. Hereby, we highlight these exciting microfluidic applications to platelet mechanobiology and platelet–circulatory system interplay as implicated in thrombosis. Last but not least, we discuss the need for microfluidic standardization and summarize the commercially available microfluidic platforms for researchers to obtain reproducible and consistent results in the field.

More homologies among the vertebrate plasma proteins

1985 ◽  
Vol 5 (10-11) ◽  
pp. 877-884 ◽  
Author(s):  
R. F. Doolittle
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Von Willebrand Factor ◽  
Unknown Function ◽  
Plasma Proteins ◽  
Common Ancestry ◽  
High Molecular Weight Kininogen ◽  
A Minor ◽  
Von Willebrand ◽  
Willebrand Factor

Many of the proteins of vertebrate blood plasma share common ancestry. As more sequences are reported, the network of relationships continues to expand in unexpected directions. Computer analysis now reveals that a minor plasma protein of unknown function, gamma-trace protein, is related to the kininogen family. Some other possible relationships have been uncovered also, including a resemblance between the histidine-rich hinge regions of high molecular weight kininogen and hemopexin and between Factor VIII and Von Willebrand Factor.

Binding of von Willebrand factor and plasma proteins to the eggshell of Schistosoma mansoni

2014 ◽  
Vol 44 (5) ◽  
pp. 263-268 ◽  
Author(s):  
Saskia deWalick ◽  
Paul J. Hensbergen ◽  
Michiel L. Bexkens ◽  
Christina Grosserichter-Wagener ◽  
Cornelis H. Hokke ◽  
...  
Keyword(s):  
Schistosoma Mansoni ◽  
Von Willebrand Factor ◽  
Plasma Proteins ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Plasma membrane phosphatidylinositol (4,5)-bisphosphate promotes Weibel–Palade body exocytosis

2020 ◽  
Vol 3 (11) ◽  
pp. e202000788
Author(s):  
Tu Thi Ngoc Nguyen ◽  
Sophia N Koerdt ◽  
Volker Gerke
Keyword(s):  
Plasma Membrane ◽  
Von Willebrand Factor ◽  
Membrane Lipids ◽  
Phospholipid Composition ◽  
Dominant Negative ◽  
Interaction Sites ◽  
Membrane Contact Sites ◽  
Phospholipase D1 ◽  
Von Willebrand ◽  
Willebrand Factor

Weibel–Palade bodies (WPB) are specialized secretory organelles of endothelial cells that control vascular hemostasis by regulated, Ca2+-dependent exocytosis of the coagulation-promoting von-Willebrand factor. Some proteins of the WPB docking and fusion machinery have been identified but a role of membrane lipids in regulated WPB exocytosis has so far remained elusive. We show here that the plasma membrane phospholipid composition affects Ca2+-dependent WPB exocytosis and von-Willebrand factor release. Phosphatidylinositol (4,5)-bisphosphate [PI(4,5)P2] becomes enriched at WPB–plasma membrane contact sites at the time of fusion, most likely downstream of phospholipase D1-mediated production of phosphatidic acid (PA) that activates phosphatidylinositol 4-phosphate (PI4P) 5-kinase γ. Depletion of plasma membrane PI(4,5)P2 or down-regulation of PI4P 5-kinase γ interferes with histamine-evoked and Ca2+-dependent WPB exocytosis and a mutant PI4P 5-kinase γ incapable of binding PA affects WPB exocytosis in a dominant-negative manner. This indicates that a unique PI(4,5)P2-rich environment in the plasma membrane governs WPB fusion possibly by providing interaction sites for WPB-associated docking factors.

Release from Intracellular Stores Is Responsible for Calcium Signaling with von Willebrand Factor in Human Platelets

2002 ◽  
Vol 87 (04) ◽  
pp. 699-705 ◽  
Author(s):  
Elizabeth Milner ◽  
Qi Zheng ◽  
John Kermode
Keyword(s):  
Plasma Membrane ◽  
Intracellular Calcium ◽  
Von Willebrand Factor ◽  
Extracellular Calcium ◽  
Lag Phase ◽  
Minor Role ◽  
Calcium Stores ◽  
Intracellular Calcium Stores ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryInteraction of von Willebrand factor (VWF) with the platelet promotes hemostasis upon vascular injury. Such interaction raises intracellular free calcium concentration ([Ca2+]i) and induces platelet activation. The platelet [Ca2+]i increase is generally attributed to influx across the plasma membrane. The present study defined the contribution of intracellular calcium stores. Platelet [Ca2+]i was monitored with Fura-PE3. Ristocetin-mediated binding of VWF transiently elevated [Ca2+]i after a lag phase. Studies with 63 healthy donors consistently revealed a VWF-induced platelet [Ca2+]i signal in the absence of extracellular calcium; there was only modest enhancement with extracellular calcium. Blockade of plasma membrane calcium channels did not diminish the signal, whereas depletion or blockade of the intracellular calcium stores abolished it. These findings imply that release from intracellular stores is responsible for the VWF-induced platelet [Ca2+]i increase. Influx across the plasma membrane plays no more than a minor role, probably representing “capacitative entry” to refill the intracellular stores.

Phospholipase D1 is specifically required for regulated secretion of von Willebrand factor from endothelial cells

Blood ◽  
2009 ◽  
Vol 113 (4) ◽  
pp. 973-980 ◽  
Author(s):  
Jennifer Disse ◽  
Nicolas Vitale ◽  
Marie-France Bader ◽  
Volker Gerke
Keyword(s):  
Endothelial Cells ◽  
Plasma Membrane ◽  
Von Willebrand Factor ◽  
Inflammatory Responses ◽  
Endothelial Activation ◽  
Tissue Type ◽  
Type Plasminogen Activator ◽  
Phospholipase D1 ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractEndothelial cells regulate thrombosis, hemostasis, and inflammatory responses by supplying the vasculature with several factors that include procoagulant von Willebrand factor (VWF) and fibrinolytic tissue-type plasminogen activator (tPA). Both proteins can be secreted in a Ca2+-regulated manner after endothelial activation but exhibit opposing physiologic effects. In search for factors that could modulate endothelial responses by selectively affecting the secretion of procoagulant or anticoagulant proteins, we identify here phospholipase D1 (PLD1) as a specific regulator of VWF secretion. PLD1 is translocated to the plasma membrane upon stimulation of endothelial secretion, and this process correlates with the generation of phosphatidic acid (PA) in the plasma membrane. Histamine-evoked secretion of VWF, but not tPA, is inhibited by blocking PLD-mediated production of PA, and this effect can be attributed to PLD1 and not PLD2. Thus, different mechanisms appear to control the agonist-induced secretion of VWF and tPA, with only the former requiring PLD1.

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