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Am J Physiol Cell Physiol 285: C797-C805, 2003. First published June 4, 2003; doi:10.1152/ajpcell.00165.2003
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RECEPTORS AND SIGNAL TRANSDUCTION

Role for phosphoinositide 3-kinase in Fc{gamma}RIIA-induced platelet shape change

Kurt L. Barkalow,1 Hervé Falet,1 Joseph E. Italiano, Jr.,1 Andrew van Vugt,2 Christopher L. Carpenter,2 Alan D. Schreiber,3 and John H. Hartwig1

1Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston 02115; and 2Beth Israel Deaconess Medical Center, Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115; and 3Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Submitted 25 April 2003 ; accepted in final form 29 May 2003

Platelets transform from disks to irregular spheres, grow filopodia, form ruffles, and spread on surfaces coated with anti-Fc{gamma}RIIA antibody. Fc{gamma}RIIA cross-linking leads to a tenfold increase in actin filament barbed end exposure and robust actin assembly. Activation of the small GTPases Rac and Cdc42 follows Fc{gamma}RIIA cross-linking. Shape change, actin filament barbed end exposure, and quantifiable actin assembly require phosphoinositide 3-kinase (PI3-kinase) activity and a rise in intracellular calcium. PI3-kinase inhibition blocks activation of Rac, but not of Cdc42, and diminishes the association of Arp2/3 complex and CapZ with polymerized actin. Furthermore, addition of constitutively active D-3 phosphorylated polyphosphoinositides or recombinant PI3-kinase subunits to octylglucoside-permeabilized platelets elicits actin filament barbed end exposure by releasing gelsolin and CapZ from the cytoskeleton. Our findings place PI3-kinase activity upstream of Rac, gelsolin, and Arp2/3 complex activation induced by Fc{gamma}RIIA and clearly distinguish the Fc{gamma}RIIA signaling pathway to actin filament assembly from the thrombin receptor protease-activated receptor (PAR)-1 pathway.

actin assembly; CD32A


Address for reprint requests and other correspondence: H. Falet, Division of Hematology, Brigham and Women's Hospital, 221 Long-wood Ave., EBRC 301, Boston, MA 02115 (E-mail: hfalet{at}rics.bwh.harvard.edu).






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