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First published online 25 January 2005
doi: 10.1242/jcs.01648

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Integrin-dependent interaction of lipid rafts with the actin cytoskeleton in activated human platelets

¹ Inserm U.563, Centre de Physiopathologie de Toulouse Purpan, Department of Oncogenesis and Signaling in Haematopoïetic Cells, IFR30, Hôpital Purpan, 31059 Toulouse, France
² Laboratoire d'Hématologie, CHU Purpan, 31059 Toulouse, France
³ Inserm U.311, Etablissement Français du Sang-Alsace, 10 Rue Spielman, BP 36, 67065 Strasbourg, France

^* Author for correspondence (e-mail: payrastr{at}toulouse.inserm.fr)

Accepted 16 November 2004

Dynamic connections between actin filaments and the plasma membrane are crucial for the regulation of blood platelet functions. Protein complexes associated with IIbß3 integrin-based cytoskeleton structures are known to play a role in these processes. However, mechanisms involving lateral organizations of the plasma membrane remain to be investigated. Here, we demonstrate that a large fraction of platelet lipid rafts specifically associates with the actin cytoskeleton upon activation. This association was inhibited by antagonists of fibrinogen-IIbß3 binding and did not occur in type I Glanzman's thrombasthenic platelets. The raft-cytoskeleton interaction is a reversible process correlating with the intensity and stability of platelet aggregation. Although only a minor fraction of IIbß3 was recovered in rafts upon activation, this integrin specifically upregulated the level of PtdIns(4,5)P₂ in membrane microdomains and induced the recruitment of several actin-modulating proteins known to directly or indirectly interact with this lipid. Controlled disruption of rafts did not affect IIbß3-mediated platelet aggregation in response to high concentrations of thrombin but significantly inhibited fibrin clot retraction. We propose that rafts participate in the organization of membrane-cytoskeleton interactions where IIbß3-mediated tension forces apply during the late phase of platelet activation.

Key words: Platelets, Lipid rafts, Actin, Cytoskeleton, Integrins, Phosphoinositides

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