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IIb
3 signals lead to cofilin to accelerate platelet actin dynamics
1 Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA
2 Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA; INSERM U428, Paris, France
3 INSERM U428, Paris, France
4 INSERM U428, Paris, France; CNRS UMR7131, Paris, France
* To whom correspondence should be addressed. E-mail: hfalet{at}rics.bwh.harvard.edu.
Cofilin, in its Ser-3 dephosphorylated form, accelerates actin filament turnover in cells. We report here the role of cofilin in platelet actin assembly. Cofilin is primarily phosphorylated in the resting platelet, as evidenced by a specific antibody directed against its Ser-3 phosphorylated form. Following stimulation with thrombin under non-stirring conditions, cofilin is reversibly dephosphorylated and transiently incorporates into the actin cytoskeleton. Its dephosphorylation is maximal 1-2 min after platelet stimulation, shortly after the peak of actin assembly occurs. Cofilin rephosphorylation begins 2 min after activation and exceeds resting levels by 5-10 min. Cofilin is dephosphorylated with identical kinetics, but fails to become rephosphorylated when platelets are stimulated under stirring conditions. Cofilin is normally rephosphorylated when platelets are stimulated in the presence of RGDS peptide or wortmannin to block 
IIb
3 cross-linking and signaling, or in platelets isolated from a patient with Glanzmann's thrombasthenia, who expresses only 2-3% of normal IIb3 levels. Furthermore, actin assembly and Arp2/3 complex incorporation into the platelet actin cytoskeleton are decreased when IIb3 is engaged. Our results suggest that cofilin is essential for actin dynamics mediated by outside-in signals in activated platelets.
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