Cofilin-mediated F-actin severing is regulated by the Rap GTPase and controls the cytoskeletal dynamics that drive lymphocyte spreading and BCR microcluster formation

Spencer A. Freeman, Victor Lei, May Dang-Lawson, Kensaku Mizuno, Calvin D. Roskelley, Michael R. Gold

    研究成果: Article査読

    63 被引用数 (Scopus)

    抄録

    When lymphocytes encounter APCs bearing cognate Ag, they spread across the surface of the APC to scan for additional Ags. This is followed by membrane contraction and the formation of Ag receptor microclusters that initiate the signaling reactions that lead to lymphocyte activation. Breakdown of the submembrane cytoskeleton is likely to be required for the cytoskeleton reorganization that drives cell spreading and for removing physical barriers that limit Ag receptor mobility. In this report, we show that Ag receptor signaling via the Rap GTPases promotes the dephosphorylation and activation of the actin-severing protein cofilin and that this results in increased severing of cellular actin filaments. Moreover, we show that this cofilin-mediated actin severing is critical for the changes in actin dynamics that drive B and T cell spreading, for the formation of BCR microclusters, and for the increased mobility of BCR microclusters within the plasma membrane after BCR engagement. Finally, using a model APC, we show that activation of this Rap-cofilin signaling module controls the amount of Ag that is gathered into BCR microclusters and that this is directly related to the magnitude of the resulting BCR signaling that is initiated during B cell-APC interactions. Thus, Rapdependent activation of cofilin is critical for the early cytoskeletal changes and BCR reorganization that are involved in APCdependent lymphocyte activation.

    本文言語English
    ページ(範囲)5887-5900
    ページ数14
    ジャーナルJournal of Immunology
    187
    11
    DOI
    出版ステータスPublished - 2011 12 1

    ASJC Scopus subject areas

    • 免疫アレルギー学
    • 免疫学

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