Alterations in the intrinsic properties of the GPIbα–VWF tether bond define the kinetics of the platelet-type von Willebrand disease mutation, Gly233Val

Doggett, Teresa A.; Girdhar, Gaurav; Lawshé, Avril; Miller, Jonathan L.; Laurenzi, Ian J.; Diamond, Scott L.; Diacovo, Thomas G.

doi:10.1182/blood-2003-01-0072

Cited by 57 publications

(61 citation statements)

References 37 publications

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“…5). These results are consistent with their respective GOF and loss of function phenotypes found in other assays, explaining the spontaneous binding of VWF to platelet for type 2B VWD (50,51) and ptVWD (42)(43)(44), as well as the ineffective binding of VWF to platelet for type 2M VWD (22,52) …”

Section: Discussionsupporting

confidence: 79%

“…We also studied a ptVWD mutant GPIb␣ (G233V) captured from lysates of G233V CHO␣␤9 cells. Consistent with its GOF phenotype in other assays (42)(43)(44), the lifetime versus force curve of 1238-A1 bonds with GPIb␣G233V (Fig. 5C, black) was significantly upshifted relative to that with WT GPIb␣ (Fig.…”

Section: Soluble Gln 1238 -Glu 1260 Reduces Gpib␣ Bond Lifetimes Withsupporting

confidence: 65%

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The N-terminal Flanking Region of the A1 Domain Regulates the Force-dependent Binding of von Willebrand Factor to Platelet Glycoprotein Ibα

Ju¹,

Dong

Crúz

et al. 2013

Journal of Biological Chemistry

196

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Section: Discussionsupporting

confidence: 79%

Section: Soluble Gln 1238 -Glu 1260 Reduces Gpib␣ Bond Lifetimes Withsupporting

confidence: 65%

The N-terminal Flanking Region of the A1 Domain Regulates the Force-dependent Binding of von Willebrand Factor to Platelet Glycoprotein Ibα

Ju¹,

Dong

Crúz

et al. 2013

Journal of Biological Chemistry

196

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“…27,34 The dissociation rate constants of transient tethers to wtDЈA3 were of the same order of magnitude as reported, although previous studies used isolated bacterial A1 domains at lower shear rates. 27,35,36 Interestingly, no significant difference in the dissociation rate constants for bonds formed between platelets and OLG mutants were detected compared with wtDЈA3. This excludes an effect of OLG on VWF-platelet dissociation as an explanation for the increased translocation rates.…”

Section: Org Frommentioning

confidence: 99%

O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions

Nowak

Canis

Riddell

et al. 2012

Blood

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AbstractWe have examined the effect of the O-linked glycan (OLG) structures of VWF on its interaction with the platelet receptor glycoprotein Ibα. The 10 OLGs were mutated individually and as clusters (Clus) on either and both sides of the A1 domain: Clus1 (N-terminal side), Clus2 (C-terminal side), and double cluster (DC), in both full-length-VWF and in a VWF construct spanning D′ to A3 domains. Mutations did not alter VWF secretion by HEK293T cells, multimeric structure, or static collagen binding. The T1255A, Clus1, and DC variants caused increased ristocetin-mediated GPIbα binding to VWF. Platelet translocation rate on OLG mutants was increased because of reduced numbers of GPIbα binding sites but without effect on bond lifetime. In contrast, OLG mutants mediated increased platelet capture on collagen under high shear stress that was associated with increased adhesion of these variants to the collagen under flow. These findings suggest that removal of OLGs increases the flexibility of the hinge linker region between the D3 and A1 domain, facilitating VWF unfolding by shear stress, thereby enhancing its ability to bind collagen and capture platelets. These data demonstrate an important functional role of VWF OLGs under shear stress conditions.

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“…2a). It has been shown that the probability P a for a cell to tether before it flows a distance x over the surface is: 11 (1) where the probability p ad for a cell to tether per unit distance is: 21 (2) where ϕ is the collision frequency and 2πrl c t c = 〈A i t i 〉 is cross-correlation of contact area and contact time. Tether rate (TR) is defined as the ratio of the number of tethering events to the total number of cells flowing through the field of view of length L in a given period (e.g., 1 min).…”

Section: Conceptual Scheme Of Tethering Processmentioning

confidence: 99%

Mechanisms for Flow-Enhanced Cell Adhesion

et al. 2008

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Cell adhesion is mediated by specific receptor-ligand bonds. In several biological systems, increasing flow has been observed to enhance cell adhesion despite the increasing dislodging fluid shear forces. Flow-enhanced cell adhesion includes several aspects: flow augments the initial tethering of flowing cells to a stationary surface, slows the velocity and increases the regularity of rolling cells, and increases the number of rollingly adherent cells. Mechanisms for this intriguing phenomenon may include transport-dependent acceleration of bond formation and force-dependent deceleration of bond dissociation. The former includes three distinct transport modes: sliding of cell bottom on the surface, Brownian motion of the cell, and rotational diffusion of the interacting molecules. The latter involves a recently demonstrated counterintuitive behavior called catch bonds where force prolongs rather than shortens the lifetimes of receptor-ligand bonds. In this article, we summarize our recently published data that used dimensional analysis and mutational analysis to elucidate the above mechanisms for flow-enhanced leukocyte adhesion mediated by L-selectinligand interactions.

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Alterations in the intrinsic properties of the GPIbα–VWF tether bond define the kinetics of the platelet-type von Willebrand disease mutation, Gly233Val

Abstract: Platelet-type von Willebrand disease (PT-VWD

Cited by 57 publications

References 37 publications

The N-terminal Flanking Region of the A1 Domain Regulates the Force-dependent Binding of von Willebrand Factor to Platelet Glycoprotein Ibα

The N-terminal Flanking Region of the A1 Domain Regulates the Force-dependent Binding of von Willebrand Factor to Platelet Glycoprotein Ibα

O-linked glycosylation of von Willebrand factor modulates the interaction with platelet receptor glycoprotein Ib under static and shear stress conditions

Mechanisms for Flow-Enhanced Cell Adhesion

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