Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases.
The complement and immunoglobulin receptors are the major phagocytic receptors involved during infection. However, only immunoglobulin-dependent uptake results in a respiratory burst and an inflammatory response in macrophages. Rho guanosine triphosphatases (molecular switches that control the organization of the actin cytoskeleton) were found to be essential for both types of phagocytosis. Two distinct mechanisms of phagocytosis were identified: Type I, used by the immunoglobulin receptor, is mediated by Cdc42 and Rac, and type II, used by the complement receptor, is mediated by Rho. These results suggest a molecular basis for the different biological consequences that are associated with phagocytosis.
Caron
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Medical Research Council Laboratory for Molecular Cell Biology, Cancer Research Campaign Oncogene and Signal Transduction Group, and Department of Biochemistry, University College London, Gower Street, London WC1E 6BT, UK.
Hall
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D016475:3T3 Cells; D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000276:immunology* / Q000378:metabolism; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D019556:COS Cells; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D004789:Enzyme Activation; D004912:Erythrocytes / Q000276:immunology; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009895:Opsonin Proteins; D010587:Phagocytosis; D010588:Phagosomes / Q000201:enzymology; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D014162:Transfection; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins
D000199:Actins; D015703:Antigens, CD; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D018797:Cell Cycle Proteins; C080568:Fc gamma receptor IIA; D016177:Macrophage-1 Antigen; D009895:Opsonin Proteins; D017452:Receptors, IgG; C031815:toxB protein, Clostridium difficile; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins