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Etude fonctionnelle de la signalisation intracellulaire médiée par l'intégrine alphaIIbbeta3 au cours de l'interaction avec le fibrinogène immobilisé

Abstract : The platelet fibrinogen (fg) receptor integrin alphaIIbbeta3 plays a major role in platelet adhesion and platelet aggregation. Fibrinogen binding to integrin alphaIIbbeta3 is complicated since 2 recognition sites have been described: the universal tripeptide RGD site and a HHLGGAKQAGDV dodecapeptide sequence. However, it is still unclear whether these 2 recognition sites function independently, synergistically, or competitively. Here we have investigated the respective role of the dodecapeptide sequence and the RGD motif in the molecular events leading to ligand-induced alphaIIbbeta3-dependent CHO cell or human platelet spreading, by using intact fg, and well-characterized plasmin-generated fg fragments containing either the RGD motif (fragment C) or the dodecapeptide site (fragment D), and CHO cells expressing resting wt, constitutively active or non-functional receptors.Our data provide evidence that alphaIIbbeta3-dependent cell adhesion to immobilized fg is a two-step process: the dodecapeptide site by itself is first able to promote cell attachment by initiating alphaIIbbeta3 clustering, FAK phosphorylation and Rac1 activation while the RGD motif subsequently acts as a molecular switch on the beta3 subunit leading to mature focal adhesion formation, maximal RhoA activation, actin cytoskeleton organization and full cell spreading.
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https://hal.univ-lorraine.fr/tel-01748069
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Submitted on : Thursday, March 29, 2018 - 11:23:23 AM
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  • HAL Id : tel-01748069, version 1

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Alexandre Salsmann. Etude fonctionnelle de la signalisation intracellulaire médiée par l'intégrine alphaIIbbeta3 au cours de l'interaction avec le fibrinogène immobilisé. Biologie moléculaire. Université Henri Poincaré - Nancy 1, 2006. Français. ⟨NNT : 2006NAN10001⟩. ⟨tel-01748069⟩

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