Elucidation of a Novel Signaling Pathway Involving PLD2 and Grb2 in WASp Mediated Phagocytosis

Abstract

<p>Wiskott‐Aldrich Syndrome Protein (WASp) is a 502‐amino acid protein within hematopoietic cells of the immune system which has been shown to be integral in cellular activities involving reorganization of the cytoskeleton, such as phagocytosis. Although the structure of WASp and activity of WASp’s role in the cytoskeleton is understood, its regulation and localization by other proteins has remained an unclear area of interest. We here demonstrate for the first time that: (1) WASp and PLD2 bind together through the adaptor Grb2 to form a heterotrimer in cells of hematopoietic lineages; (2) the resultant heterotrimer is formed in response to complement receptor ligation, which also localizes the heterotrimer to the site of the filopodia; (3) the heterotrimer serves as a mechanism through which WASp is delivered and activated at the filopodia via membranous PIP2; and (4) that PLD2 is responsible for both acting as an upstream regulator for WASp activation and a membranous anchor which localizes activated WASp to the filopodia. We speculate that this novel heterotrimer is a crucial mechanism through which WASp is able to be activated only after delivery to the membrane, where actin nucleation can occur and the phagocytic cup can be formed during initial engulfment.</p><p>This presentation occurred at the Wright State University Campus-Wide Celebration of Research, Scholarship and Creative Activities on April 8, 2011</p>