An essential function for the calcium-promoted Ras inactivator in Fcgamma receptor-mediated phagocytosis.
Fc receptor (FcR)-mediated phagocytosis requires activation of the Rho GTPases Cdc42 and Rac1, but how they are recruited to the FcR is unknown. Here we show that the calcium-promoted Ras inactivator (CAPRI), a Ras GTPase-activating protein, functions as an adaptor for Cdc42 and Rac1 during FcR-mediated phagocytosis. CAPRI-deficient macrophages had impaired FcgammaR-mediated phagocytosis and oxidative burst, as well as defective activation of Cdc42 and Rac1. CAPRI interacted constitutively with both Cdc42 and Rac1 and translocated to phagocytic cups during FcgammaR-mediated phagocytosis. CAPRI-deficient mice had an impaired innate immune response to bacterial infection. These results suggest that CAPRI provides a link between FcgammaR and Cdc42 and Rac1 and is essential for innate immune responses.
Zhang
Jun
J
Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Guo
Jian
J
Dzhagalov
Ivan
I
He
You-Wen
YW
D000818:Animals; D001424:Bacterial Infections / Q000276:immunology / Q000378:metabolism; D001853:Bone Marrow / Q000276:immunology; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D010587:Phagocytosis; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D051193:Toll-Like Receptors; D020764:cdc42 GTP-Binding Protein / Q000276:immunology* / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000276:immunology* / Q000378:metabolism; D020703:ras GTPase-Activating Proteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*
D008562:Membrane Glycoproteins; C504471:Rasa4 protein, mouse; D011956:Receptors, Cell Surface; D017452:Receptors, IgG; D051193:Toll-Like Receptors; D020703:ras GTPase-Activating Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein