scholarly journals The ADAMTS metalloproteinases

2005 ◽  
Vol 386 (1) ◽  
pp. 15-27 ◽  
Author(s):  
Sarah PORTER ◽  
Ian M. CLARK ◽  
Lara KEVORKIAN ◽  
Dylan R. EDWARDS
Keyword(s):  
Von Willebrand Factor ◽  
Structural Organization ◽  
Altered Expression ◽  
Functional Roles ◽  
Pathological Conditions ◽  
The Matrix ◽  
Inhibition Of Angiogenesis ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Human Family

The ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs) are a group of proteases that are found both in mammals and invertebrates. Since the prototype ADAMTS-1 was first described in 1997, there has been a rapidly expanding body of literature describing this gene family and the proteins they encode. The complete human family has 19 ADAMTS genes, together with three members of a newly identified subgroup, the ADAMTSL (ADAMTS-like) proteins, which have several domains in common with the ADAMTSs. The ADAMTSs are extracellular, multidomain enzymes whose known functions include: (i) collagen processing as procollagen N-proteinase; (ii) cleavage of the matrix proteoglycans aggrecan, versican and brevican; (iii) inhibition of angiogenesis; and (iv) blood coagulation homoeostasis as the von Willebrand factor cleaving protease. Roles in organogenesis, inflammation and fertility are also apparent. Recently, some ADAMTS genes have been found to show altered expression in arthritis and various cancers. This review highlights progress in understanding the structural organization and functional roles of the ADAMTSs in normal and pathological conditions.

scholarly journals von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1531-1534 ◽  
Author(s):  
LA Sporn ◽  
VJ Marder ◽  
DD Wagner
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Immunofluorescent Staining ◽  
Cultured Endothelial Cells ◽  
Human Foreskin Fibroblasts ◽  
Platelet Binding ◽  
The Matrix ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.

scholarly journals Absence of tubular structures and immunolabeling for von Willebrand factor in the platelet alpha-granules from porcine von Willebrand disease [published erratum appears in Blood 1987 Feb;69(2):707]

Blood ◽  
1986 ◽  
Vol 68 (3) ◽  
pp. 774-778 ◽  
Author(s):  
EM Cramer ◽  
JP Caen ◽  
L Drouet ◽  
J Breton-Gorius
Keyword(s):  
Von Willebrand Factor ◽  
Human Platelets ◽  
Von Willebrand Disease ◽  
Tubular Structures ◽  
Electron Microscopic ◽  
Dense Part ◽  
The Matrix ◽  
Cytoplasmic Microtubules ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract The electron microscopic localization of von Willebrand factor (vWF) was studied in platelets from normal and von Willebrand disease (vWD) pigs. In normal pig platelets, immunolabeling for vWF was far more intense and extensive than in human platelets and was either localized at one pole of the alpha-granule or all along its periphery or long axis. As in human platelets, this immunolabeling coincided with the presence of tubules about 200 nm in diameter. These structures were more numerous than in human platelets, with up to 30 tubules per alpha- granule. They were easily identified either in transverse sections, usually grouped in a less electron-dense part of the matrix at one pole of the alpha-granule, or in longitudinal sections parallel to the long axis of the elongated granules, or coiled around the alpha-granule core. They closely resemble those structures found in Weibel-Palade bodies. In platelets from pigs with severe vWD, these structures were absent, as was the immunolabeling for vWF; however, cytoplasmic microtubules were normally present in these platelets. Thus, the granule-associated tubules can be distinguished from the microtubules, which are larger in diameter (250 nm), are present in both normal and vWD platelets, and do not stain for vWF. These results strongly suggest that the tubular structures present in the alpha-granules of normal porcine platelets correspond to the vWF molecule itself.

scholarly journals Structure of Plasmodium falciparum TRAP (thrombospondin-related anonymous protein) A domain highlights distinct features in apicomplexan von Willebrand factor A homologues

2013 ◽  
Vol 450 (3) ◽  
pp. 469-476 ◽  
Author(s):  
Tero Pihlajamaa ◽  
Tommi Kajander ◽  
Juho Knuuti ◽  
Kaisa Horkka ◽  
Amit Sharma ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Von Willebrand Factor ◽  
Metal Ion ◽  
Cell Attachment ◽  
Protein A ◽  
Site Directed Mutagenesis ◽  
Mammalian Host ◽  
Functional Roles ◽  
Von Willebrand ◽  
Willebrand Factor

TRAP (thrombospondin-related anonymous protein), localized in the micronemes and on the surface of sporozoites of the notorious malaria parasite Plasmodium, is a key molecule upon infection of mammalian host hepatocytes and invasion of mosquito salivary glands. TRAP contains two adhesive domains responsible for host cell recognition and invasion, and is known to be essential for infectivity. In the present paper, we report high-resolution crystal structures of the A domain of Plasmodium falciparum TRAP with and without bound Mg2+. The structure reveals a vWA (von Willebrand factor A)-like fold and a functional MIDAS (metal-ion-dependent adhesion site), as well as a potential heparan sulfate-binding site. Site-directed mutagenesis and cell-attachment assays were used to investigate the functional roles of the surface epitopes discovered. The reported structures are the first determined for a complete vWA domain of parasitic origin, highlighting unique features among homologous domains from other proteins characterized hitherto. Some of these are conserved among Plasmodiae exclusively, whereas others may be common to apicomplexan organisms in general.

scholarly journals Functional Roles of the von Willebrand Factor Propeptide

2021 ◽  
Vol 41 (01) ◽  
pp. 063-068
Author(s):  
Orla Rawley ◽  
David Lillicrap
Keyword(s):  
Von Willebrand Factor ◽  
Wound Repair ◽  
Structural Features ◽  
Functional Roles ◽  
Rgd Sequence ◽  
Physiological Processes ◽  
Large Size ◽  
Disulfide Linkages ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractThe primary polypeptide sequence of von Willebrand factor (VWF) includes an N-terminal 741-amino acid VWF propeptide (VWFpp). In cells expressing VWF, the VWFpp performs two critical functions. In the Golgi, VWFpp mediates the intermolecular disulfide linkages that generate high-molecular-weight VWF multimers. Subsequently, the VWFpp, which is proteolytically cleaved from mature VWF by furin, functions to generate the endothelial storage organelles (Weibel-Palade bodies) in which VWF and a distinct collection of proteins are stored, and from where they undergo regulated secretion from the endothelium. The VWFpp is secreted from endothelial cells as dimers and circulates in plasma with at least some of the dimers associating with a noncovalent manner with the D′D3 domain of mature VWF. The VWFpp has a half-life of 2 to 3 hours in plasma, but to date no extracellular function has been determined for the molecule. Nevertheless, its large size and several biologically interesting structural features (two sets of vicinal cysteines and an RGD sequence) suggest that there may be roles that the VWFpp plays in hemostasis or associated physiological processes such as angiogenesis or wound repair.

Clinical significance of determination of ADAMTS-13 metalloproteinase, its inhibitor, and von Willebrand factor in neonatal pathological conditions

2019 ◽  
Vol 11_2019 ◽  
pp. 74-81
Author(s):  
Bitsadze V.O. Bitsadze ◽  
Grigoryeva K.N. Grigoryeva ◽  
Ilalami I. Ilalami ◽  
Makatsariya A.D. Makatsariya ◽  
Mingalimov M.A. Mingalimov ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Von Willebrand Factor ◽  
Pathological Conditions ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Perturbation of human endothelial cells by thrombin or PMA changes the reactivity of their extracellular matrix towards platelets.

1987 ◽  
Vol 104 (3) ◽  
pp. 697-704 ◽  
Author(s):  
P G de Groot ◽  
J H Reinders ◽  
J J Sixma
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
De Novo ◽  
The Matrix ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Adhesion Of Platelets ◽  
De Novo Protein Synthesis

In this study we have examined the influence of perturbation of endothelial cells on the amounts of fibronectin and von Willebrand factor in their extracellular matrix and the consequences of a changed composition of the matrix on platelet adhesion. For this purpose, we have used an in vitro perfusion system with which we can investigate the interactions of platelets in flowing blood with cultured endothelial cells and their extracellular matrix (Sakariassen, K. S., P. A. M. M. Aarts, P. G. de Groot, W. P. M. Houdgk, and J. J. Sixma, 1983, J. Lab. Clin Med. 102:522-535). Treatment of endothelial cells with 0.1-1.0 U/ml thrombin for 2 h increased the reactivity of the extracellular matrix, isolated after the thrombin treatment, towards platelets by approximately 50%. The increased reactivity did not depend on de novo protein synthesis but was inhibited by 3-deazaadenosine, an inhibitor of phospholipid methylation, which also inhibits the stimulus-induced instantaneous release of von Willebrand factor from endothelial cells. However, no changes in the amounts of von Willebrand factor and fibronectin in the matrix were detected. Thrombin may change the organization of the matrix proteins, not the composition. When endothelial cells were perturbed with the phorbol ester PMA or thrombin for 3 d, the adhesion of platelets to the extracellular matrix of treated cells was strongly impaired. This impairment coincided with a decrease in the amounts of von Willebrand factor and fibronectin present in the matrix. These results indicate that, after perturbation, endothelial cells regulate the composition of their matrix, and that this regulation has consequences for the adhesion of platelets.

von Willebrand factor released from Weibel-Palade bodies binds more avidly to extracellular matrix than that secreted constitutively

Blood ◽  
1987 ◽  
Vol 69 (5) ◽  
pp. 1531-1534 ◽  
Author(s):  
LA Sporn ◽  
VJ Marder ◽  
DD Wagner
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Von Willebrand Factor ◽  
Immunofluorescent Staining ◽  
Cultured Endothelial Cells ◽  
Human Foreskin Fibroblasts ◽  
Platelet Binding ◽  
The Matrix ◽  
Von Willebrand ◽  
Willebrand Factor

Large multimers of von Willebrand factor (vWf) are released from the Weibel-Palade bodies of cultured endothelial cells following treatment with a secretagogue (Sporn et al, Cell 46:185, 1986). These multimers were shown by immunofluorescent staining to bind more extensively to the extracellular matrix of human foreskin fibroblasts than constitutively secreted vWf, which is composed predominantly of dimeric molecules. Increased binding of A23187-released vWf was not due to another component present in the releasate, since releasate from which vWf was adsorbed, when added together with constitutively secreted vWf, did not promote binding. When iodinated plasma vWf was overlaid onto the fibroblasts, the large forms bound preferentially to the matrix. These results indicated that the enhanced binding of the vWf released from the Weibel-Palade bodies was likely due to its large multimeric size. It appears that multivalency is an important component of vWf interaction with the extracellular matrix, just as has been shown for vWf interaction with platelets. The pool of vWf contained within the Weibel-Palade bodies, therefore, is not only especially suited for platelet binding, but also for interaction with the extracellular matrix.

Cultured Endothelial Cells Regulate Platelet Adhesion to their Extracellular Matrix by Regulating its von Willebrand Factor Content

1995 ◽  
Vol 73 (04) ◽  
pp. 713-718 ◽  
Author(s):  
Ya-Ping Wu ◽  
Jan J Sixma ◽  
Philip G de Groot
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Serum Concentration ◽  
Von Willebrand Factor ◽  
Culture Medium ◽  
Culture Conditions ◽  
The Matrix ◽  
Passage Number ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryEndothelial cells and their extracellular matrix formed in vitro are often used as a model for subendothelium in studies on platelet-vessel wall interaction. We have characterized the influence of culture conditions of endothelial cells on the formation of extracellular matrix and on the interaction of the matrix with platelets. Passage number, time of confluence, serum concentration and the addition of heparin, growth factors and antibiotics to the culture medium were varied and the extracellular matrices were isolated. The amount of fibronectin and von Willebrand factor present in the matrix were measured and the number of platelets adhering to these matrices after perfusion with citrated whole blood at a shear rate of 1000 s-l was determined. A three times increase of the amount of von Willebrand factor in the matrix was found when the serum concentration was increased from 2.5% to 30%. When the passage number of the cells was increased or the period during which the cells were at confluence was extended, the amount of von Willebrand factor in the matrix was decreased up to 50%. Addition of heparin or ECGS (endothelial cell growth supplement) decreased the von Willebrand factor content in the matrix. Addition of penicillin or streptomycin to the culture medium had no influence on the amount of von Willebrand factor deposited in the matrix or secreted into the medium, however, other antibiotics such as gentamycin and neomycin decrease the amount of von Willebrand factor in the matrix. No influence on the amount of fibronectin in the matrix was found under all conditions tested.There was a strong correlation between the amount of von Willebrand factor in the matrix and the number of platelets adhering to the matrix. A decrease or increase of the amount of von Willebrand factor was always correlated with a decrease or increase of the number of platelets adhering to the matrix. These results indicate that the synthesis and deposition of von Willebrand factor in the extracellular matrix by cultured endothelial cells is very sensitive to variations in culture conditions and that the amount of von Willebrand factor in the matrix predominantly determines the reactivity of the matrix for platelets.

Sign in / Sign up

Export Citation Format

Share Document