scholarly journals Arf GTPase-Activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor

Biology Open ◽  
2021 ◽  
Author(s):  
Asano Watanabe ◽  
Hikari Hataida ◽  
Naoya Inoue ◽  
Kosuke Kamon ◽  
Keigo Baba ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Secretory Granules ◽  
The Other ◽  
Negative Regulators ◽  
Histamine Stimulation ◽  
Gtpase Activating Proteins ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Hydrolysis Of

Arf GTPase-Activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors (Arfs), that are critical to form transport intermediates. ArfGAPs have been thought to be negative regulators of Arfs, however, accumulating evidence indicates that ArfGAPs are important for cargo sorting and promote membrane traffic. Weibel-Palade bodies (WPBs) are cigar-shaped secretory granules in endothelial cells that contain von Willebrand factor (vWF) as their main cargo. WPB biogenesis at the Golgi was reported to be regulated by Arf and their regulators, but the role of ArfGAPs has been unknown. In this study, we performed siRNA screening of ArfGAPs to investigate the role of ArfGAPs in the biogenesis of WPBs. We found two ArfGAPs, SMAP1 and AGFG2, to be involved in WPB size and vWF exocytosis, respectively. SMAP1 depletion resulted in small-sized WPBs, and the lysosomal inhibitor leupeptin recovered the size of WPBs. The results indicate that SMAP1 functions in preventing the degradation of cigar-shaped WPBs. On the other hand, AGFG2 downregulation resulted in the inhibition of vWF secretion upon Phorbol 12-myristate 13-acetate (PMA) or histamine stimulation, suggesting that AGFG2 plays a role in vWF exocytosis. Our study revealed unexpected roles of ArfGAPs in vWF transport.

scholarly journals Arf GTPase-Activating proteins SMAP1 and AGFG2 regulate the size of Weibel-Palade bodies and exocytosis of von Willebrand factor

2021 ◽  
Author(s):  
Asano Watanabe ◽  
Hikari Hataida ◽  
Naoya Inoue ◽  
Kosuke Kamon ◽  
Keigo Baba ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Intracellular Transport ◽  
Secretory Granules ◽  
Secretory Proteins ◽  
Adp Ribosylation ◽  
Gtpase Activating Proteins ◽  
Summary Statement ◽  
Golgi Network ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractArf GTPase-Activating proteins (ArfGAPs) mediate the hydrolysis of GTP bound to ADP-ribosylation factors, which are important for intracellular transport. ArfGAPs have been shown to be critical for cargo sorting in the Golgi-to-ER and post-Golgi traffic. However, their roles in the sorting of secretory proteins remains unclear. Weibel-Palade bodies (WPBs) are cigar-shaped secretory granules in endothelial cells that contain von Willebrand factor (vWF) as their main cargo. WPBs are formed at the trans-Golgi Network, and this process is thought to be coupled with the sorting of vWF. WPB biogenesis was reported to be regulated by ADP-ribosylation factors and their regulators, but the role of ArfGAPs has been unknown. In this study, we performed siRNA screening of ArfGAPs to investigate the biogenesis of WPBs. We found two ArfGAPs, SMAP1 and AGFG2, to be involved in WPB size and vWF exocytosis, respectively. SMAP1 depletion resulted in small-sized WPBs, and the lysosomal inhibitor leupeptin recovered the size of WPBs. These results indicate that SMAP1 functions in preventing the degradation of cigar-shaped WPBs. However, AGFG2 downregulation resulted in the inhibition of vWF secretion upon Phorbol 12-myristate 13-acetate (PMA)-stimulation, suggesting that AGFG2 plays a role in vWF exocytosis. Our study revealed unexpected processes regulated by ArfGAPs for vWF transport.Summary StatementThe ArfGAP proteins SMAP1 and AGFG2 were identified as regulating WPB size and vWF exocytosis.

scholarly journals The role of von Willebrand factor in breast cancer metastasis

2021 ◽  
Vol 14 (4) ◽  
pp. 101033
Author(s):  
Chia Yin Goh ◽  
Sean Patmore ◽  
Albert Smolenski ◽  
Jane Howard ◽  
Shane Evans ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Von Willebrand Factor ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Von Willebrand ◽  
Willebrand Factor

Role of Platelet Membrane Glycoproteins and Von Willebrand Factor in Adhesion of Platelets to Subendothelium and Collagen

1987 ◽  
Vol 516 (1 Blood in Cont) ◽  
pp. 52-65 ◽  
Author(s):  
KJELL S. SAKARIASSEN ◽  
EDITH FRESSINAUD ◽  
JEAN-PIERRE GIRMA ◽  
DOMINIQUE MEYER ◽  
HANS R. BAUMGARTNER
Keyword(s):  
Von Willebrand Factor ◽  
Platelet Membrane ◽  
Membrane Glycoproteins ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Adhesion Of Platelets

scholarly journals Partial characterization of a binding site for von Willebrand factor on glycocalicin

Blood ◽  
1986 ◽  
Vol 67 (1) ◽  
pp. 19-26 ◽  
Author(s):  
AD Michelson ◽  
J Loscalzo ◽  
B Melnick ◽  
BS Coller ◽  
RI Handin
Keyword(s):  
Binding Site ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Binding Activity ◽  
Proteolytic Fragment ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Beta Galactosidase

The binding of von Willebrand factor (vWF) to platelet membrane glycoprotein Ib (GpIb) facilitates platelet adhesion to vascular subendothelium. In this study, we provide evidence that the vWF binding site is on glycocalicin (GC), a proteolytic fragment of GpIb, and we examine the role of the carbohydrate portion of GC on that binding. The binding to platelets of 6D1, a monoclonal antibody that recognizes an epitope on GpIb and blocks ristocetin-induced vWF binding to platelets, was inhibited by purified GC. In addition, purified GC inhibited ristocetin-dependent binding of 125I-labeled vWF to platelets. Since GC contains 60% carbohydrate by weight, we assessed the role of carbohydrate sequences on its interaction with antibody 6D1 and vWF. Based on the known sequence of the major oligosaccharide chain of GC--N- acetyl neuraminic acid, galactose, N-acetyl glucosamine, N-acetyl galactosamine--we treated GC sequentially with neuraminidase, beta- galactosidase, and beta-N-acetylglucosaminidase. Removal of sialic acid and galactose residues did not affect GC binding. Removal of N-acetyl glucosamine residues did not affect GC binding to 6D1 but did decrease the ability of GC to inhibit vWF binding to platelets, increasing the concentration needed to inhibit binding by 50% (IC50) 40-fold. This suggests that a portion of the oligosaccharide chains on GC contributes to the vWF binding activity of this molecule.

scholarly journals Platelet von Willebrand factor: evidence for its involvement in platelet adhesion to collagen

Blood ◽  
1987 ◽  
Vol 70 (4) ◽  
pp. 1214-1217
Author(s):  
E Fressinaud ◽  
D Baruch ◽  
C Rothschild ◽  
HR Baumgartner ◽  
D Meyer
Keyword(s):  
Shear Rate ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Von Willebrand Disease ◽  
High Shear ◽  
Shear Rates ◽  
High Shear Rates ◽  
Von Willebrand ◽  
Willebrand Factor

Although it is well established that plasma von Willebrand Factor (vWF) is essential to platelet adhesion to subendothelium at high shear rates, the role of platelet vWF is less clear. We studied the respective role of both plasma and platelet vWF in mediating platelet adhesion to fibrillar collagen in a parallel-plate perfusion chamber. Reconstituted blood containing RBCs, various mixtures of labeled washed platelets and plasma from controls or five patients with severe von Willebrand disease (vWD), was perfused through the chamber for five minutes at a shear rate of 1,600 s-1. Platelet-collagen interactions were estimated by counting the radioactivity in deposited platelets and by quantitative morphometry. When the perfusate consisted of normal platelets suspended in normal plasma, platelet deposition on the collagen was 24.7 +/- 3.6 X 10(6)/cm2 (mean +/- SEM, n = 6). Significantly less deposition (16 +/- 2.3) was observed when vWD platelets were substituted for normal platelets. In mixtures containing vWD plasma, significantly greater deposition (9 +/- 2.2) was obtained with normal than with vWD platelets (1 +/- 0.4) demonstrating a role for platelet vWF in mediating the deposition of platelets on collagen. Morphometric analysis confirmed these data. Our findings indicate that platelet, as well as plasma, vWF mediates platelet-collagen interactions at a high shear rate.

scholarly journals Regulation of plasma von Willebrand factor

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 96 ◽  
Author(s):  
Karl C Desch
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Coagulation Factor ◽  
Vascular Wall ◽  
Healthy Human ◽  
Venous Thromboembolic ◽  
Artery Disease ◽  
Von Willebrand ◽  
Willebrand Factor

Von Willebrand factor (VWF) is a multimeric plasma glycoprotein that plays a central role in the initiation of blood coagulation. Through interactions between its specific functional domains, the vascular wall, coagulation factor VIII, and platelet receptors, VWF maintains hemostasis by binding to platelets and delivering factor VIII to the sites of vascular injury. In the healthy human population, plasma VWF levels vary widely. The important role of VWF is illustrated by individuals at the extremes of the normal distribution of plasma VWF concentrations where individuals with low VWF levels are more likely to present with mucocutaneous bleeding. Conversely, people with high VWF levels are at higher risk for venous thromboembolic disease, stroke, and coronary artery disease. This report will summarize recent advances in our understanding of environmental influences and the genetic control of VWF plasma variation in healthy and symptomatic populations and will also highlight the unanswered questions that are currently driving this field of study.

scholarly journals Predictors of Bleeding from Esophageal Varices: The Role of Factor VII and von Willebrand Factor (vWF)

2014 ◽  
Vol 04 (04) ◽  
pp. 152-158 ◽  
Author(s):  
Ali Abdelrahman Ghweil ◽  
Usama Ahmed Arafa ◽  
Ashraf Khodeary ◽  
Ahmed N. Salem
Keyword(s):  
Von Willebrand Factor ◽  
Esophageal Varices ◽  
Factor Vii ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Successful management of multiple pregnancies in a family with varying severity of Von Willebrand disease

2018 ◽  
Vol 11 (4) ◽  
pp. 192-194
Author(s):  
Patrick Harrington ◽  
Pippa Kyle ◽  
Jacky Cutler ◽  
Bella Madan
Keyword(s):  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
The Other ◽  
Severe Phenotype ◽  
Mild Phenotype ◽  
History Of ◽  
Specialist Treatment ◽  
Factor Concentrate ◽  
Von Willebrand ◽  
Willebrand Factor

We present the obstetric history of a family of three sisters with Von Willebrand disease, managed in our centre over the course of nine successful pregnancies. The abnormalities result from inheritance of an exon 50 skipping mutation in the Von Willebrand factor gene, resulting from consanguinity. Two of the sisters were identified as having a severe phenotype with a Von Willebrand factor level of less than 5 IU/dl, with the other having a mild phenotype. Of the sisters with a severe phenotype, one had a number of prenatal complications and required early onset prophylaxis with Von Willebrand factor concentrate, whilst the other had a less complicated clinical course, only requiring Von Willebrand factor concentrate to cover labour. The sister with mild Von Willebrand disease had a rise in Von Willebrand factor levels during pregnancy and required no specialist treatment. The report highlights the markedly different clinical courses that can occur in patients with Von Willebrand disease and the different approaches to management.

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