title: Integrin-dependent interaction of lipid rafts with the actin cytoskeleton in activated human platelets.
abstract: Dynamic connections between actin filaments and the plasma membrane are crucial for the regulation of blood platelet functions. Protein complexes associated with alphaIIbbeta3 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-alphaIIbbeta3 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 alphaIIbbeta3 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 alphaIIbbeta3-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 alphaIIbbeta3-mediated tension forces apply during the late phase of platelet activation.
authors.affiliation: Inserm U.563, Centre de Physiopathologie de Toulouse Purpan, Department of Oncogenesis and Signaling in Haematopoïetic Cells, IFR30, Hôpital Purpan, 31059 Toulouse, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Bodin
authors.forename: Carine
authors.initials: C
authors.lastname: Soulet
authors.forename: Hélène
authors.initials: H
authors.lastname: Tronchère
authors.forename: Pierre
authors.initials: P
authors.lastname: Sié
authors.forename: Christian
authors.initials: C
authors.lastname: Gachet
authors.forename: Monique
authors.initials: M
authors.lastname: Plantavid
authors.forename: Bernard
authors.initials: B
authors.lastname: Payrastre
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D003018:Clot Retraction; D006801:Humans; D021962:Membrane Microdomains / Q000378:metabolism / Q000502:physiology*; D008840:Microfilament Proteins / Q000378:metabolism; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000502:physiology*
chemical_list: D008840:Microfilament Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D019039:Platelet Glycoprotein GPIIb-IIIa Complex