HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/4/C819    most recent 00587.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Falet, H. Articles by Hartwig, J. H. Search for Related Content PubMed PubMed Citation Articles by Falet, H. Articles by Hartwig, J. H.

RECEPTORS AND SIGNAL TRANSDUCTION

Integrin _IIb3 signals lead cofilin to accelerate platelet actin dynamics

¹Division of Hematology, Brigham and Women’s Hospital, Department of Medicine, Harvard Medical School, Boston, Massachusetts; and ²Institut National de la Santé et de la Recherche Médicale Unité 428, Unité de Formation et de Recherche des Sciences Pharmaceutiques et Biologiques, Université René Descartes, Paris, and ³Centre National de la Recherche Scientifique Unité Mixte de Recherche 7131, Hôpital Broussais, Paris, France

Submitted 1 December 2004 ; accepted in final form 10 May 2005

Cofilin, in its Ser3 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 Ser3 phosphorylated form. After stimulation with thrombin under nonstirring 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 Arg-Gly-Asp-Ser (RGDS) peptide or wortmannin to block _IIb3 cross-linking and signaling or in platelets isolated from a patient with Glanzmann thrombasthenia, which express only 2–3% of normal _IIb3 levels. Furthermore, actin assembly and Arp2/3 complex incorporation in 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.

This article has been cited by other articles:

				C. Frantz, G. Barreiro, L. Dominguez, X. Chen, R. Eddy, J. Condeelis, M. J.S. Kelly, M. P. Jacobson, and D. L. Barber Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding J. Cell Biol., December 1, 2008; 183(5): 865 - 879. [Abstract] [Full Text] [PDF]

				C. X. Sun, M. A.O. Magalhaes, and M. Glogauer Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor J. Cell Biol., October 22, 2007; 179(2): 239 - 245. [Abstract] [Full Text] [PDF]

				B. T. Kile, A. D. Panopoulos, R. A. Stirzaker, D. F. Hacking, L. H. Tahtamouni, T. A. Willson, L. A. Mielke, K. J. Henley, J.-G. Zhang, I. P. Wicks, et al. Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia Blood, October 1, 2007; 110(7): 2371 - 2380. [Abstract] [Full Text] [PDF]

				P. C. Redondo, M. T. Harper, J. A. Rosado, and S. O. Sage A role for cofilin in the activation of store-operated calcium entry by de novo conformational coupling in human platelets Blood, February 1, 2006; 107(3): 973 - 979. [Abstract] [Full Text] [PDF]

				D. Pandey, P. Goyal, J. R. Bamburg, and W. Siess Regulation of LIM-kinase 1 and cofilin in thrombin-stimulated platelets Blood, January 15, 2006; 107(2): 575 - 583. [Abstract] [Full Text] [PDF]