Surface recruitment but not activation of integrin αIIbβ3 (GPIIb-IIIa) requires a functional actin cytoskeleton

John B. Addo, Paul F. Bray, Dmitriy Grigoryev, Nauder Faraday, Pascal Goldschmidt-Clermont

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Binding of integrin αIIbβ3 (glycoprotein [GP] IIb-IIIa) to soluble fibrinogen requires that the receptor undergo a conformational change (receptor activation), which occurs rapidly in agonist-stimulated platelets. Agonist stimulation of platelets also results in αIIbβ3 recruitment from intracellular membranes (α-granules and open canalicular system) to the platelet surface. Once activated and accessible, the receptor can engage, a process that corresponds to the binding of the receptor to its soluble fibrinogen ligand, leading to intracellular signaling reactions and centripetal migration of bound receptor molecules. Because these processes occur concurrently with a marked reorganization of the actin cytoskeleton, we investigated the role of actin in fibrinogen receptor activation and surface recruitment. We used a flow cytometric assay to directly quantitate the binding of αIIbβ3 to fluorescently labeled fibrinogen on the platelet surface. Cytochalasin D, which inhibits elongation of actin filaments, was used to prevent the actin response to platelet agonists. Despite its ability to inhibit the actin response and αIIbβ3 binding to the actin cytoskeleton, cytochalasin D did not alter the agonist-induced intramolecular changes resulting in increased affinity of αIIbβ3 for soluble fibrinogen and therefore did not inhibit ADP-induced aggregation. Thus, disruption of the actin network with cytochalasin D had no effect on the dissociation constant of the complex between activated αIIbβ3 and fibrinogen (Kd=0.26 to 0.28 μmol/L). However, cytochalasin D suppressed the recruitment of cryptic αIIbβ3 molecules to the platelet surface. While the physiological consequence of exposing additional αIIbβ3 molecules on the surface of platelets is unclear, it is tempting to speculate that this process plays an important role in consolidating intra-arterial platelet thrombi, despite the shear strain generated by the arterial blood flow.

Original languageEnglish
Pages (from-to)1466-1473
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume15
Issue number9
StatePublished - Sep 1 1995
Externally publishedYes

Fingerprint

Actin Cytoskeleton
Integrins
Blood Platelets
Cytochalasin D
Fibrinogen
Actins
Fibrinogen Receptors
Intracellular Membranes
Platelet Glycoprotein GPIIb-IIIa Complex
Adenosine Diphosphate
Thrombosis
Ligands

Keywords

  • Actin
  • Cytoskeleton
  • Fibrinogen receptor
  • Integrin
  • Platelets

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Addo, J. B., Bray, P. F., Grigoryev, D., Faraday, N., & Goldschmidt-Clermont, P. (1995). Surface recruitment but not activation of integrin αIIbβ3 (GPIIb-IIIa) requires a functional actin cytoskeleton. Arteriosclerosis, Thrombosis, and Vascular Biology, 15(9), 1466-1473.

Surface recruitment but not activation of integrin αIIbβ3 (GPIIb-IIIa) requires a functional actin cytoskeleton. / Addo, John B.; Bray, Paul F.; Grigoryev, Dmitriy; Faraday, Nauder; Goldschmidt-Clermont, Pascal.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 15, No. 9, 01.09.1995, p. 1466-1473.

Research output: Contribution to journalArticle

Addo, JB, Bray, PF, Grigoryev, D, Faraday, N & Goldschmidt-Clermont, P 1995, 'Surface recruitment but not activation of integrin αIIbβ3 (GPIIb-IIIa) requires a functional actin cytoskeleton', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 15, no. 9, pp. 1466-1473.
Addo, John B. ; Bray, Paul F. ; Grigoryev, Dmitriy ; Faraday, Nauder ; Goldschmidt-Clermont, Pascal. / Surface recruitment but not activation of integrin αIIbβ3 (GPIIb-IIIa) requires a functional actin cytoskeleton. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 1995 ; Vol. 15, No. 9. pp. 1466-1473.
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