The coordination of signaling during Fc receptor-mediated phagocytosis.
Phagocytosis by macrophages can be initiated by Fcgamma receptors (FcR) in membranes that bind to Fc regions of immunoglobulin G (IgG). Activated FcR transduce signals to cytoplasm, which regulate the internalization of IgG-coated particles into plasma membrane-derived vacuoles, phagosomes. Particles internalized by phagocytosis are much larger than FcR, which prompts questions of if and how the receptors are coordinated with each other. FcR-mediated signal transduction entails recruitment of proteins from cytoplasm to the receptor, largely via protein phosphorylation. These FcR signaling complexes then activate proteins that regulate actin, myosin, membrane fusion, and the production of reactive oxygen intermediates. Recent fluorescence microscopic studies of phagocytosis in macrophages indicate that signaling by FcR occurs as a sequence of distinct stages, evident in the spatial and temporal patterns of phosphoinositides, protein kinase C, and Rho-family GTPase activation on forming phagosomes. The coordination of these stages may be regulated by lipids or lipid-anchored proteins, which diffuse away from FcR complexes. Lateral diffusion of FcR-derived signals could integrate FcR-dependent responses over large areas of membrane in the forming phagosome.
University of Michigan Medical School, 1335 Catherine Street, Med Sci II, Rm. 5608, Ann Arbor, MI 48109-0620, USA. jswan@umich.edu
Joel A
JA
Swanson
Adam D
AD
Hoppe
D000818:Animals; D002462:Cell Membrane / Q000276:immunology; D004058:Diffusion; D004789:Enzyme Activation / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D010587:Phagocytosis / Q000276:immunology*; D021381:Protein Transport / Q000276:immunology; D011961:Receptors, Fc / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology*
D007074:Immunoglobulin G; D011961:Receptors, Fc