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An essential function for the calcium-promoted Ras inactivator in Fcγ receptor–mediated phagocytosis

Nature Immunology volume 6, pages 911–919 (2005)Cite this article

Abstract

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 FcγR-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 FcγR-mediated phagocytosis. CAPRI-deficient mice had an impaired innate immune response to bacterial infection. These results suggest that CAPRI provides a link between FcγR and Cdc42 and Rac1 and is essential for innate immune responses.

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Figure 1: Generation of CAPRI-deficient mice.
Figure 2: Impaired bacterial clearance in CAPRI-deficient mice.
Figure 3: Defective FcγR-mediated phagocytosis by CAPRI-deficient macrophages.
Figure 4: Defective phagocytic cup formation and oxidative burst in CAPRI-deficient macrophages.
Figure 5: Regulation of Cdc42 and Rac1 activity by CAPRI.
Figure 6: CAPRI interacts with Cdc42 and Rac1.
Figure 7: Interaction of CAPRI deletion mutants with Cdc42 and Rac1 and 'rescue' of CAPRI deficiency by active Cdc42 and Rac1.
Figure 8: The effect of CAPRI deficiency on the activation of Erk, Syk and Cbl.

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Acknowledgements

This work was initiated in the laboratory of M.J. Bevan (University of Washington, Seattle, Washington), whom we thank for support; we also thank W. Zhang, M. Krangel, J. Poe and H. Hartig for critical review of this manuscript. Supported by the National Institutes of Health (AI54685 and CA92123) and American Cancer Society (RSG-0125201 to Y.-W.H.).

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  1. Jun Zhang and Jian Guo: These authors contributed equally to this work.

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  1. Department of Immunology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    Jun Zhang, Jian Guo, Ivan Dzhagalov & You-Wen He

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  1. Jun Zhang
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Correspondence to You-Wen He.

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Supplementary information

Supplementary Fig. 1

cDNA sequence of mouse CAPRI and its protein translation. (PDF 78 kb)

Supplementary Fig. 2

Activation of CAPRI-deficient macrophages by PAMPs and bacteria. (PDF 104 kb)

Supplementary Methods (PDF 53 kb)

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Zhang, J., Guo, J., Dzhagalov, I. et al. An essential function for the calcium-promoted Ras inactivator in Fcγ receptor–mediated phagocytosis. Nat Immunol 6, 911–919 (2005). https://doi.org/10.1038/ni1232

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