Fig. 1

Model of FcγR signaling and microclustering relative to actin and pseudopod extension. a FcγR ligation by IgG drives phosphorylation of ITAMs and subsequent recruitment of signaling proteins including Syk and PI3K. Fluorescent labeling of IgG (red star) allowed observation of IgG-FcγR complexes relative to the recruitment of Syk or BtkPH (gold stars) which specifically binds the PI3K product, PI(3,4,5)P₃. b-c Frustrated phagocytosis in response to IgG-presented on a supported lipid bilayer is shown schematically. The zipper model, which describes macrophage engulfment of IgG-coated particles, suggests FcγR-IgG interaction occurs through sequential engagement of new receptors during the advancement of the phagosome. Activated FcγRs (blue) cluster and are initially driven forward by polymerizing actin (purple, b). These complexes then disengage from the polymerizing actin and move toward the center of the cell by attaching to retrograde actin (green, c). New FcγR complexes form as new FcγR bind IgG at the leading edge (grey). The arrows indicate the direction of the polymerizing actin, retrograde actin and the associated FcγR cluster movement