TAILIEUCHUNG - Báo cáo khoa học: Distinct but critical roles for integrin aIIbb3 in platelet lamellipodia formation on fibrinogen, collagen-related peptide and thrombin

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. | ễFEBS Journal Distinct but critical roles for integrin aIIbp3 in platelet lamellipodia formation on fibrinogen collagen-related peptide and thrombin Kelly Thornber1 Owen J. T. McCarty2 3 Steve P. Watson2 and Catherine J. Pears1 1 Department of Biochemistry University of Oxford UK 2 Centre for Cardiovascular Sciences Institute of BiomedicalResearch University of Birmingham UK 3 Department of BiomedicalEngineering Oregon Health Science University Portland OR USA Keywords aIIbp3 adhesion integrins lamellipodia platelets Correspondence C. Pears Department of Biochemistry South Parks Road University of Oxford Oxford OX1 3QU UK Fax 44 1865 275259 Tel 44 1865 275737 E-mail Website http Received 11 July 2006 revised 22 August 2006 accepted 12 September 2006 doi 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 aIIbp3 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 aIIbb3 ligand fibrinogen. Nevertheless lamelli-podia formation on collagen-related peptide and thrombin is dependent upon engagement of aIIbb3 consistent with release of aIIbb3 ligand s from platelet granules. However the requirement for

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