The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells

Yuping Yuan, Suhasini Kulkarni, Philippe Ulsemer, Susan L. Cranmer, Cindy L. Yap, Warwick S. Nesbitt, Ian Harper, Nayna Mistry, Sacha M. Dopheide, Sascha C. Hughan, David Williamson, Corinne De La Salle, Hatem H. Salem, Francois Lanza, Shaun P. Jackson

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Abstract

Platelet adhesion to sites of vascular injury is initiated by the binding of the platelet glycoprotein (GP) Ib-V-IX complex to matrix-bound yon Willebrand factor (vWf). This receptor-ligand interaction is characterized by a rapid on-off rate that enables efficient platelet tethering and rolling under conditions of rapid blood flow. We demonstrate here that platelets adhering to immobilized vWf under flow conditions undergo rapid morphological conversion from fiat discs to spiny spheres during surface translocation. Studies of Glanzmann thrombasthenic platelets (lacking integrin α(IIb)β3) and Chinese hamster ovary (CHO) cells transfected with GPIb/IX (CHO-Ib/IX) confirmed that vWf binding to GPIb/IX was sufficient to induce actin polymerization and cytoskeletal reorganization independent of integrin α(IIb)β3. vWf-induced cytoskeletal reorganization occurred independently of several well characterized signaling processes linked to platelet activation, including calcium influx, prostaglandin metabolism, protein tyrosine phosphorylation, activation of protein kinase C or phosphatidylinositol 3-kinase but was critically dependent on the mobilization of intracellular calcium. Studies of Oregon Green 488 1,2-bis(o- amino-5-fluorophenoxy)ethane-N,N,N',N-tetraacetic acid tetraacetoxymethyl ester-loaded platelets and CHO-Ib/IX cells demonstrated that these cells mobilize intracellular calcium in a shear-dependent manner during surface translocation on vWf. Taken together, these studies suggest that the vWf-GPIb interaction stimulates actin polymerization and cytoskeletal reorganization in rolling platelets via a shear-sensitive signaling pathway linked to intracellular calcium mobilization.

Original languageEnglish
Pages (from-to)36241-36251
Number of pages11
JournalJournal of Biological Chemistry
Volume274
Issue number51
DOIs
Publication statusPublished - 17 Dec 1999

Cite this

Yuan, Yuping ; Kulkarni, Suhasini ; Ulsemer, Philippe ; Cranmer, Susan L. ; Yap, Cindy L. ; Nesbitt, Warwick S. ; Harper, Ian ; Mistry, Nayna ; Dopheide, Sacha M. ; Hughan, Sascha C. ; Williamson, David ; De La Salle, Corinne ; Salem, Hatem H. ; Lanza, Francois ; Jackson, Shaun P. / The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 51. pp. 36241-36251.
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title = "The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells",
abstract = "Platelet adhesion to sites of vascular injury is initiated by the binding of the platelet glycoprotein (GP) Ib-V-IX complex to matrix-bound yon Willebrand factor (vWf). This receptor-ligand interaction is characterized by a rapid on-off rate that enables efficient platelet tethering and rolling under conditions of rapid blood flow. We demonstrate here that platelets adhering to immobilized vWf under flow conditions undergo rapid morphological conversion from fiat discs to spiny spheres during surface translocation. Studies of Glanzmann thrombasthenic platelets (lacking integrin α(IIb)β3) and Chinese hamster ovary (CHO) cells transfected with GPIb/IX (CHO-Ib/IX) confirmed that vWf binding to GPIb/IX was sufficient to induce actin polymerization and cytoskeletal reorganization independent of integrin α(IIb)β3. vWf-induced cytoskeletal reorganization occurred independently of several well characterized signaling processes linked to platelet activation, including calcium influx, prostaglandin metabolism, protein tyrosine phosphorylation, activation of protein kinase C or phosphatidylinositol 3-kinase but was critically dependent on the mobilization of intracellular calcium. Studies of Oregon Green 488 1,2-bis(o- amino-5-fluorophenoxy)ethane-N,N,N',N-tetraacetic acid tetraacetoxymethyl ester-loaded platelets and CHO-Ib/IX cells demonstrated that these cells mobilize intracellular calcium in a shear-dependent manner during surface translocation on vWf. Taken together, these studies suggest that the vWf-GPIb interaction stimulates actin polymerization and cytoskeletal reorganization in rolling platelets via a shear-sensitive signaling pathway linked to intracellular calcium mobilization.",
author = "Yuping Yuan and Suhasini Kulkarni and Philippe Ulsemer and Cranmer, {Susan L.} and Yap, {Cindy L.} and Nesbitt, {Warwick S.} and Ian Harper and Nayna Mistry and Dopheide, {Sacha M.} and Hughan, {Sascha C.} and David Williamson and {De La Salle}, Corinne and Salem, {Hatem H.} and Francois Lanza and Jackson, {Shaun P.}",
year = "1999",
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language = "English",
volume = "274",
pages = "36241--36251",
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The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells. / Yuan, Yuping; Kulkarni, Suhasini; Ulsemer, Philippe; Cranmer, Susan L.; Yap, Cindy L.; Nesbitt, Warwick S.; Harper, Ian; Mistry, Nayna; Dopheide, Sacha M.; Hughan, Sascha C.; Williamson, David; De La Salle, Corinne; Salem, Hatem H.; Lanza, Francois; Jackson, Shaun P.

In: Journal of Biological Chemistry, Vol. 274, No. 51, 17.12.1999, p. 36241-36251.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The von Willebrand factor-glycoprotein Ib/V/IX interaction induces actin polymerization and cytoskeletal reorganization in rolling platelets and glycoprotein Ib/V/IX-transfected cells

AU - Yuan, Yuping

AU - Kulkarni, Suhasini

AU - Ulsemer, Philippe

AU - Cranmer, Susan L.

AU - Yap, Cindy L.

AU - Nesbitt, Warwick S.

AU - Harper, Ian

AU - Mistry, Nayna

AU - Dopheide, Sacha M.

AU - Hughan, Sascha C.

AU - Williamson, David

AU - De La Salle, Corinne

AU - Salem, Hatem H.

AU - Lanza, Francois

AU - Jackson, Shaun P.

PY - 1999/12/17

Y1 - 1999/12/17

N2 - Platelet adhesion to sites of vascular injury is initiated by the binding of the platelet glycoprotein (GP) Ib-V-IX complex to matrix-bound yon Willebrand factor (vWf). This receptor-ligand interaction is characterized by a rapid on-off rate that enables efficient platelet tethering and rolling under conditions of rapid blood flow. We demonstrate here that platelets adhering to immobilized vWf under flow conditions undergo rapid morphological conversion from fiat discs to spiny spheres during surface translocation. Studies of Glanzmann thrombasthenic platelets (lacking integrin α(IIb)β3) and Chinese hamster ovary (CHO) cells transfected with GPIb/IX (CHO-Ib/IX) confirmed that vWf binding to GPIb/IX was sufficient to induce actin polymerization and cytoskeletal reorganization independent of integrin α(IIb)β3. vWf-induced cytoskeletal reorganization occurred independently of several well characterized signaling processes linked to platelet activation, including calcium influx, prostaglandin metabolism, protein tyrosine phosphorylation, activation of protein kinase C or phosphatidylinositol 3-kinase but was critically dependent on the mobilization of intracellular calcium. Studies of Oregon Green 488 1,2-bis(o- amino-5-fluorophenoxy)ethane-N,N,N',N-tetraacetic acid tetraacetoxymethyl ester-loaded platelets and CHO-Ib/IX cells demonstrated that these cells mobilize intracellular calcium in a shear-dependent manner during surface translocation on vWf. Taken together, these studies suggest that the vWf-GPIb interaction stimulates actin polymerization and cytoskeletal reorganization in rolling platelets via a shear-sensitive signaling pathway linked to intracellular calcium mobilization.

AB - Platelet adhesion to sites of vascular injury is initiated by the binding of the platelet glycoprotein (GP) Ib-V-IX complex to matrix-bound yon Willebrand factor (vWf). This receptor-ligand interaction is characterized by a rapid on-off rate that enables efficient platelet tethering and rolling under conditions of rapid blood flow. We demonstrate here that platelets adhering to immobilized vWf under flow conditions undergo rapid morphological conversion from fiat discs to spiny spheres during surface translocation. Studies of Glanzmann thrombasthenic platelets (lacking integrin α(IIb)β3) and Chinese hamster ovary (CHO) cells transfected with GPIb/IX (CHO-Ib/IX) confirmed that vWf binding to GPIb/IX was sufficient to induce actin polymerization and cytoskeletal reorganization independent of integrin α(IIb)β3. vWf-induced cytoskeletal reorganization occurred independently of several well characterized signaling processes linked to platelet activation, including calcium influx, prostaglandin metabolism, protein tyrosine phosphorylation, activation of protein kinase C or phosphatidylinositol 3-kinase but was critically dependent on the mobilization of intracellular calcium. Studies of Oregon Green 488 1,2-bis(o- amino-5-fluorophenoxy)ethane-N,N,N',N-tetraacetic acid tetraacetoxymethyl ester-loaded platelets and CHO-Ib/IX cells demonstrated that these cells mobilize intracellular calcium in a shear-dependent manner during surface translocation on vWf. Taken together, these studies suggest that the vWf-GPIb interaction stimulates actin polymerization and cytoskeletal reorganization in rolling platelets via a shear-sensitive signaling pathway linked to intracellular calcium mobilization.

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U2 - 10.1074/jbc.274.51.36241

DO - 10.1074/jbc.274.51.36241

M3 - Article

VL - 274

SP - 36241

EP - 36251

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 51

ER -