An Essential Role for Talin during αMβ2-mediated Phagocytosis

J Lim, A Wiedemann, G Tzircotis… - Molecular biology of …, 2007 - Am Soc Cell Biol
J Lim, A Wiedemann, G Tzircotis, SJ Monkley, DR Critchley, E Caron
Molecular biology of the cell, 2007Am Soc Cell Biol
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, αMβ2 integrin) and not through the Fc γ …
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, αMβ2 integrin) and not through the Fc γ receptor. We show that talin physically interacts with CR3/αMβ2 and that this interaction involves the talin head domain and residues W747 and F754 in the β2 integrin cytoplasmic domain. The CR3/αMβ2–talin head interaction controls not only talin recruitment to forming phagosomes but also CR3/αMβ2 binding 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/αMβ2 receptor and phagocytic uptake.
Am Soc Cell Biol