Identification and analysis of copine/BONZAI proteins among evolutionarily diverse plant species

Genome ◽  
2016 ◽  
Vol 59 (8) ◽  
pp. 565-573 ◽  
Author(s):  
Baohong Zou ◽  
Xuexue Hong ◽  
Yuan Ding ◽  
Xiang Wang ◽  
He Liu ◽  
...  
Keyword(s):  
Plant Species ◽  
Protein Localization ◽  
Calcium Dependent ◽  
Functional Studies ◽  
Phylogeny Analysis ◽  
Genome Wide ◽  
Evolutionarily Conserved ◽  
Von Willebrand ◽  
Diverse Plant Species ◽  
Willebrand Factor

Copines are evolutionarily conserved calcium-dependent membrane-binding proteins with potentially critical biological functions. In plants, the function of these proteins has not been analyzed except for in Arabidopsis thaliana where they play critical roles in development and disease resistance. To facilitate functional studies of copine proteins in crop plants, genome-wide identification, curation, and phylogeny analysis of copines in 16 selected plant species were conducted. All the identified 32 plant copines have conserved features of the two C2 domains (C2A and C2B) and the von Willebrand factor A (vWA) domain. Different from animal and protozoa copines, plant copines have glycine at the second residue potentially acquiring a unique protein myristoylation modification. Phylogenetic analysis suggests that copine was present as one copy when evolving from green algae to basal flowering plants, and duplicated before the divergence of monocots and dicots. In addition, gene expression and protein localization study of rice copines suggests both conserved and different properties of copines in dicots and monocots. This study will contribute to uncovering the role of copine genes in different plant species.

Impaired adhesion of neutrophils expressing Slc44a2/HNA-3b to VWF protects against NETosis under venous shear rate

Blood ◽  
2021 ◽  
Author(s):  
Gaia Zirka ◽  
Philippe Robert ◽  
Julia Tilburg ◽  
Victoria Tishkova ◽  
Chrissta X Maracle ◽  
...  
Keyword(s):  
Transmembrane Protein ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Wild Type ◽  
Shear Rates ◽  
Extracellular Traps ◽  
Genome Wide ◽  
Healthy Donors ◽  
Von Willebrand ◽  
Willebrand Factor

Genome wide association studies linked expression of the human neutrophil antigen 3b (HNA-3b) epitope on the Slc44a2 protein with a 30% decreased risk of venous thrombosis (VT) in humans. Slc44a2 is a ubiquitous transmembrane protein identified as a receptor for Von Willebrand factor (VWF). To explain the link between Slc44a2 and VT we wanted to determine how Slc44a2 expressing either HNA-3a or HNA-3b on neutrophils could modulate their adhesion and activation on VWF under flow. Transfected HEK293T cells or neutrophils homozygous for the HNA-3a- or the HNA-3b-coding allele were purified from healthy donors and perfused in flow chambers coated with VWF at venous shear rates (100s-1). HNA-3a expression was required for Slc44a2-mediated neutrophil adhesion to VWF at 100s-1. This adhesion could occur independently of β2 integrin and was enhanced when neutrophils are preactivated with lipopolysaccharide (LPS). Moreover, specific shear conditions with high neutrophil concentration could act as a "second hit", inducing the formation of neutrophil extracellular traps. Neutrophil mobilization was also measured by intravital microscopy in venules from SLC44A2-knockout and wild-type mice after histamine-induced endothelial degranulation. Mice lacking Slc44a2 showed a massive reduction in neutrophil recruitment in inflamed mesenteric venules. Our results show that Slc44a2/HNA-3a is important for the adhesion and activation of neutrophils in veins under inflammation and when submitted to specific shears. Neutrophils expressing Slc44a2/HNA-3b not being associated with these observations, these results could thus explain the association between HNA-3b and a reduced risk for VT in humans.

scholarly journals Common and Rare Variants in Genes Associated with von Willebrand Factor Level Variation: No Accumulation of Rare Variants in Swedish von Willebrand Disease Patients

TH Open ◽  
2020 ◽  
Vol 04 (04) ◽  
pp. e322-e331
Author(s):  
Eric Manderstedt ◽  
Christina Lind-Halldén ◽  
Stefan Lethagen ◽  
Christer Halldén
Keyword(s):  
Von Willebrand Factor ◽  
Rare Variants ◽  
Association Studies ◽  
Low Frequency ◽  
Von Willebrand Disease ◽  
Genome Wide Association Studies ◽  
Genome Wide ◽  
The Common ◽  
Von Willebrand ◽  
Willebrand Factor

AbstractGenome-wide association studies (GWASs) have identified genes that affect plasma von Willebrand factor (VWF) levels. ABO showed a strong effect, whereas smaller effects were seen for VWF, STXBP5, STAB2, SCARA5, STX2, TC2N, and CLEC4M. This study screened comprehensively for both common and rare variants in these eight genes by resequencing their coding sequences in 104 Swedish von Willebrand disease (VWD) patients. The common variants previously associated with the VWF level were all accumulated in the VWD patients compared to three control populations. The strongest effect was detected for blood group O coded for by the ABO gene (71 vs. 38% of genotypes). The other seven VWF level associated alleles were enriched in the VWD population compared to control populations, but the differences were small and not significant. The sequencing detected a total of 146 variants in the eight genes. Excluding 70 variants in VWF, 76 variants remained. Of the 76 variants, 54 had allele frequencies > 0.5% and have therefore been investigated for their association with the VWF level in previous GWAS. The remaining 22 variants with frequencies < 0.5% are less likely to have been evaluated previously. PolyPhen2 classified 3 out of the 22 variants as probably or possibly damaging (two in STAB2 and one in STX2); the others were either synonymous or benign. No accumulation of low frequency (0.05–0.5%) or rare variants (<0.05%) in the VWD population compared to the gnomAD (Genome Aggregation Database) population was detected. Thus, rare variants in these genes do not contribute to the low VWF levels observed in VWD patients.

Dibucaine-Activated Platelet Protease(S) Digests GPIb-EDTA Only Partially Inhibits

1981 ◽  
Author(s):  
Barry S Coller
Keyword(s):  
Protease Activity ◽  
Shape Change ◽  
Initial Slope ◽  
Short Term ◽  
Release Reaction ◽  
Calcium Dependent ◽  
Total Inhibition ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Ristocetin Cofactor

Local anesthetics have been reported to have several effects on platelets including: 1) inhibition of shape change, the release reaction and aggregation induced by several agents 2) dissolution of cytoskeletal structures and 3) activation of a protease activity which digests proteins of Mr 250,000 and 230,000. It was speculated that the last effect may be due to the Ca++-dependent protease previously described in platelets. I have recently observed that incubation of platelets with 1 mM dibucaine for brief periods of time (15-30 min) resulted in 50-100% enhancement of the initial slope of agglutination induced by either ristocetin or bovine von Willebrand factor (vWf) despite inhibiting the release reaction. If the platelets were formaldehyde-fixed after brief incubation, they also showed the enhancement (control 23 ± 3 U/min (mean ± SEM) and dibucaine 47 ± 6, p < 0.01, n = 7 for ristocetin and 36 ± 7 vs. 65 ± 5, p < 0.01, n= 6 for bovine vWf). Using these platelets, the ristocetin cofactor assay was more sensitive and yet equally specific. If, however, fresh platelets were incubated with dibucaine for > 1 hour, both ristocetin and bovine vWf-induced agglutination became progressively inhibited with almost total inhibition after several hours. This decrease in agglutination was associated with a progressive loss of a glycoprotein with the characteristics of GpIb (Mr 165,000 unreduced and 135,000 reduced) as judged by PAS-stained polyacrylamide gels. The presence of the platelet-impenetrable calcium chelator EDTA (10 mM) only partially prevented the decrease in agglutinability and loss of Gplb. I conclude that: 1. Short term incubation with dibucaine may improve the ristocetin cofactor assay. 2. A dibucaine-activated protease(s) appears to digest Gplb, probably accounting for the decreased agglutination with long incubations. 3. If operating from the outside of the platelet after leakage, at least some of the protease activity is not calcium dependent.

scholarly journals Proteolytic cleavage of human von Willebrand factor induced by enzyme(s) released from polymorphonuclear cells

Blood ◽  
1986 ◽  
Vol 67 (5) ◽  
pp. 1281-1285
Author(s):  
EA Thompson ◽  
MA Howard
Keyword(s):  
Von Willebrand Factor ◽  
Cell Activation ◽  
Calcium Ionophore ◽  
Ionophore A23187 ◽  
Polymorphonuclear Cells ◽  
Dependent Manner ◽  
Calcium Dependent ◽  
Von Willebrand ◽  
Willebrand Factor

In vivo fragmentation of the von Willebrand factor antigen (vWF:Ag) molecule has been demonstrated on radiocrossed immunoelectrophoresis (CIE) in the plasma from patients with disseminated intravascular coagulation, in factor VIII concentrates, and in normal serum. Experiments reported here show that polymorphonuclear (PMN) cells contain a non-calcium-dependent protease(s) that when released and incubated with vWF:Ag results in an additional vWF:Ag peak on radio- CIE. Production of fragments of vWF:Ag by incubation with PMN cells occurred in a time-dependent manner. The protease(s) responsible was inhibited by diisopropyl fluorophosphate, soybean trypsin inhibitor, and aprotinin, but not by benzamidine, azide, epicron, or hirudin. Citrate, EDTA, and leupeptin also had no effect on the PMN cell enzyme's activity, indicating that the enzyme(s) is not calcium dependent. The PMN cell enzyme responsible for vWF:Ag fragmentation is located intracellularly and released by freezethaw lysis or cell activation by calcium or the calcium ionophore A23187.

scholarly journals Genome-Wide Association Transethnic Meta-Analyses Identifies Novel Associations Regulating Coagulation Factor VIII and von Willebrand Factor Plasma Levels

Circulation ◽  
2019 ◽  
Vol 139 (5) ◽  
pp. 620-635 ◽  
Author(s):  
Maria Sabater-Lleal ◽  
Jennifer E. Huffman ◽  
Paul S. de Vries ◽  
Jonathan Marten ◽  
Michael A. Mastrangelo ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Plasma Levels ◽  
Coagulation Factor ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Meta Analyses ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Novel Associations

FURTHER EVIDENCES OF VON WILLEBRAND FACTOR INVOLVEMENT IN THROMBOTIC THROMBOCYTOPENIC PURPURA (TTP)

1987 ◽  
Author(s):  
J Chediak ◽  
J Eldridge ◽  
D Sobel ◽  
B Maxey ◽  
J Baron ◽  
...  
Keyword(s):  
Von Willebrand Factor ◽  
Response To Therapy ◽  
Severe Thrombocytopenia ◽  
Laboratory Findings ◽  
Calcium Dependent ◽  
Normal Individuals ◽  
Excessive Consumption ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Acute Event

Laboratory findings of TTP include severe thrombocytopenia and marked anemia due to intravascular hemolysis. The pathogenesis of the thrombocytopenia is poorly understood. Possible mechanisms include the presence of a platelet aggregating factor (JCI 76:1330, 1935), a calcium dependent protease (Blood 63:310a, 1986), abnormal prostaglandin production or metabolism, and an excessive consumption of high molecular weight forms of von Uillebrand factor (VUF). Von Willebrand factor proteins from 12 patients (pts) diagnosed as having TTP were studied. They include 8 females and 4 males; nine were studied during the acute presentation and seven pts also during the remission period. Three pts died during the acute event. None of the pts had a recurrence. Control subjects include both normal individuals and thrombocytopenic pts due to a variety of underlying diseases including marrow aplasia and immune thrombocytopenia, but excluding pts with DIC or suffering infection. Plasmas were tested for VWF antigen and Ristocetin Cofactor (RiCof) activity. The electrophoretic mobility (CIE) of VWF:Ag was also assessed and the ratio VWF:RiCof to VWF:Ag was determined. Statistical analysis including p values will be reported. Results:These results suggest that during the acute event there is an excessive consumption of large VWF multimers and the ratio VWF:RiCof/VWF:Ag could be used to corroborate the diagnosis of TTP and by doing sequential measurements to monitor the response to therapy.

scholarly journals Linkage analysis identifies a locus for plasma von Willebrand factor undetected by genome-wide association

2012 ◽  
Vol 110 (2) ◽  
pp. 588-593 ◽  
Author(s):  
K. C. Desch ◽  
A. B. Ozel ◽  
D. Siemieniak ◽  
Y. Kalish ◽  
J. A. Shavit ◽  
...  
Keyword(s):  
Linkage Analysis ◽  
Von Willebrand Factor ◽  
Genome Wide Association ◽  
Genome Wide ◽  
Von Willebrand ◽  
Willebrand Factor
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