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Blood, 15 September 2002, Vol. 100, No. 6, pp. 2113-2122
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Normal Arp2/3 complex activation in platelets lacking
WASp
Hervé Falet,
Karin M. Hoffmeister,
Ralph Neujahr, and
John H. Hartwig
From the Division of Hematology, Brigham and Women's
Hospital, Department of Medicine, Harvard Medical School, Boston, MA.
Arp2/3 complex is believed to induce de novo nucleation of actin
filaments at the edge of motile cells downstream of WASp family
proteins. In this study, the signaling pathways leading to Arp2/3
complex activation, actin assembly, and shape change were investigated
in platelets isolated from patients with Wiskott-Aldrich Syndrome
(WAS), that is, who lack WASp, and in WASp-deficient mouse platelets.
WASp-deficient human and mouse platelets elaborate filopodia, spread
lamellae, and assemble actin, identical to control WASp-expressing
platelets. Human platelets contain 2 µM Arp2/3 complex, or 8600 molecules/cell. Arp2/3 complex redistributes to the edge of the
lamellae and to the Triton X-100-insoluble actin cytoskeleton of
activated WASp-deficient platelets. Furthermore, the C-terminal CA
domain of N-WASp, which sequesters Arp2/3 complex, inhibits by half the
actin nucleation capacity of octylglucoside-permeabilized and activated
WAS platelets, similar to its effect in WASp-expressing cells. Along
with WASp, platelets express WAVE-2 as a physiologic activator of
Arp2/3 complex and a small amount of N-WASp. Taken together, our
findings show that platelets activate Arp2/3 complex, assemble actin,
and change shape in the absence of WASp, indicating a more specialized
role for WASp in these cells.
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