An essential role for talin during alpha(M)beta(2)-mediated phagocytosis.
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, alpha(M)beta(2) integrin) and not through the Fc gamma receptor. We show that talin physically interacts with CR3/alpha(M)beta(2) and that this interaction involves the talin head domain and residues W747 and F754 in the beta(2) integrin cytoplasmic domain. The CR3/alpha(M)beta(2)-talin head interaction controls not only talin recruitment to forming phagosomes but also CR3/alpha(M)beta(2) 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/alpha(M)beta(2)-mediated phagocytosis, most noticeably activation of the CR3/alpha(M)beta(2) receptor and phagocytic uptake.
Lim
Jenson
J
Centre for Molecular Microbiology and Infection, Division of Cell and Molecular Biology, Imperial College London, London SW7 2AZ, United Kingdom.
Wiedemann
Agnès
A
Tzircotis
George
G
Monkley
Susan J
SJ
Critchley
David R
DR
Caron
Emmanuelle
E
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D004912:Erythrocytes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000737:chemistry / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D010587:Phagocytosis; D010649:Phenylalanine; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017452:Receptors, IgG / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012756:Sheep; D016608:Talin / Q000378:metabolism*; D014364:Tryptophan
D007074:Immunoglobulin G; D016177:Macrophage-1 Antigen; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D016608:Talin; D049452:Green Fluorescent Proteins; D010649:Phenylalanine; D014364:Tryptophan