Normal Arp2/3 complex activation in platelets lacking WASp

  • Hervé Falet
    From the Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA.
  • Karin M. Hoffmeister
    From the Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA.
  • Ralph Neujahr
    From the Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA.
  • John H. Hartwig
    From the Division of Hematology, Brigham and Women's Hospital, Department of Medicine, Harvard Medical School, Boston, MA.

書誌事項

公開日
2002-09-15
DOI
  • 10.1182/blood.v100.6.2113
公開者
American Society of Hematology

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説明

<jats:title>Abstract</jats:title><jats:p>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.</jats:p>

収録刊行物

  • Blood

    Blood 100 (6), 2113-2122, 2002-09-15

    American Society of Hematology

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