Distinct but critical roles for integrin αIIbβ 3 in platelet lamellipodia formation on fibrinogen, collagen-related peptide and thrombin

Kelly Thornber, Owen J.T. McCarty, Steve P. Watson, Catherine J. Pears

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Integrins are the major receptor type known to facilitate cell adhesion and lamellipodia formation on extracellular matrix proteins. However, collagen-related peptide and thrombin have recently been shown to mediate platelet lamellipodia formation when presented as immobilized surfaces. The aims of this study were to establish if there exists a role for the platelet integrin αIIbβ3 in this response; and if so, whether signalling from the integrin is required for lamellipodia formation on these surfaces. Real-time analysis was used to compare platelet morphological changes on surfaces of fibrinogen, collagen-related peptide or thrombin in the presence of various pharmacological inhibitors and platelets from 'knockout' mice. We demonstrate that collagen-related peptide and thrombin stimulate distinct patterns of platelet lamellipodia formation and elevation of intracellular Ca2+ to that induced by the integrin αIIbβ3 ligand, fibrinogen. Nevertheless, lamellipodia formation on collagen-related peptide and thrombin is dependent upon engagement of αIIbβ3, consistent with release of αIIbβ3 ligand(s) from platelet granules. However, the requirement for signalling by the integrin on fibrinogen can be bypassed by the addition of thrombin to the solution. These observations reveal a critical role for αIIbβ3 in forming lamellipodia on collagen-related peptide and thrombin which is dependent on its ability to function as an adhesive receptor but not necessarily on its ability to signal. These results suggest that integrins may play an important role in lamellipodia formation triggered by nonintegrin ligands in platelets and possibly in other cell types.

Original languageEnglish (US)
Pages (from-to)5032-5043
Number of pages12
JournalFEBS Journal
Volume273
Issue number22
DOIs
StatePublished - Nov 1 2006

Keywords

  • Adhesion
  • Integrins
  • Lamellipodia
  • Platelets
  • αβ

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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