An Essential Role for Talin during αMβ2-mediated Phagocytosis

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Abstract
The cytoskeletal, actin-binding protein talin has been previously implicated in phagocytosis in Dictyostelium discoideum and mammalian phagocytes. However, its mechanism of action during internalization is not understood. Our data confirm that endogenous talin can occasionally be found at phagosomes forming around IgG- and C3bi-opsonized red blood cells in macrophages. Remarkably, talin knockdown specifically abrogates uptake through complement receptor 3 (CR3, CD11b/CD18, αMβ2integrin) and not through the Fc γ receptor. We show that talin physically interacts with CR3/αMβ2and that this interaction involves the talin head domain and residues W747 and F754 in the β2integrin cytoplasmic domain. The CR3/αMβ2–talin head interaction controls not only talin recruitment to forming phagosomes but also CR3/αMβ2binding activity, both in macrophages and transfected fibroblasts. However, the talin head domain alone cannot support phagocytosis. Our results establish for the first time at least two distinct roles for talin during CR3/αMβ2-mediated phagocytosis, most noticeably activation of the CR3/αMβ2receptor and phagocytic uptake.