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Thromb Haemost 2003; 89(02): 318-330
DOI: 10.1055/s-0037-1613449
Platelets and Blood Cells
Schattauer GmbH

A critical role of lipid rafts in the organization of a key FcγRIIa-mediated signaling pathway in human platelets

Stéphane Bodin
1   Inserm, Unité 563, Centre de Physiopathologie de Toulouse Purpan, Department of Oncogenesis and Signaling in Haematopoïetic Cells, IFR30, Hôpital Purpan, Toulouse, France
,
Cécile Viala
1   Inserm, Unité 563, Centre de Physiopathologie de Toulouse Purpan, Department of Oncogenesis and Signaling in Haematopoïetic Cells, IFR30, Hôpital Purpan, Toulouse, France
,
Ashraf Ragab
1   Inserm, Unité 563, Centre de Physiopathologie de Toulouse Purpan, Department of Oncogenesis and Signaling in Haematopoïetic Cells, IFR30, Hôpital Purpan, Toulouse, France
,
Bernard Payrastre
1   Inserm, Unité 563, Centre de Physiopathologie de Toulouse Purpan, Department of Oncogenesis and Signaling in Haematopoïetic Cells, IFR30, Hôpital Purpan, Toulouse, France
› Institutsangaben
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Publikationsverlauf

Received 20. Mai 2002

Accepted after resubmission 25. Oktober 2002

Publikationsdatum:
07. Dezember 2017 (online)

    Lizenzen und Reprints

Summary

The involvement of platelet FcγRIIa in heparin-associated thrombocytopenia (HIT) is now well established. However, the precise sequence of molecular events initiated by FcγRIIa cross-linking in platelets remains partly characterized. We investigated here the role of lipid rafts in the spatio-temporal organization of the FcγRIIa-dependent signaling events. Upon cross-linking, FcγRIIa relocated in rafts where the kinase Lyn and the adapter LAT were among the major phosphotyrosyl proteins. Upon stimulation by HIT sera, the second messenger phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) accumulated in rafts in a P2Y12 adenosine diphosphate (ADP) recep- tor-dependent manner. PtdIns(3,4,5)P3 was then essential to specifically recruit phospholipase Cγ2 (PLCγ2) to these membrane microdomains. Controlled disruption of rafts by methyl γ-cyclodextrin reversibly abolished PtdIns(3,4,5)P3 production, PLC activation and platelet responses induced by FcγRIIa cross-linking without affecting the tyrosine phosphorylation events. This work demonstrates that platelet rafts are essential for the integration of a key signaling complex leading to the rapid production of PtdIns(3,4,5)P3 and in turn PLCγ2 activation during HIT.

Keywords

FcγRIIa - platelets - rafts - phosphoinositides - P2Y12
 

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