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Rho-Kinase and Myosin-II Control Phagocytic Cup Formation during CR, but Not FcγR, Phagocytosis

2002; Elsevier BV; Volume: 12; Issue: 16 Linguagem: Inglês

10.1016/s0960-9822(02)01069-2

1879-0445

Isabel M. Olazabal, Emmanuelle Caron, Robin C. May, Kerstin Schilling, David A. Knecht, Laura M. Machesky,

Protein Kinase Regulation and GTPase Signaling

Phagocytosis through Fcγ receptor (FcγR) or complement receptor 3 (CR) requires Arp2/3 complex-mediated actin polymerization, although each receptor uses a distinct signaling pathway [1Kaplan G. Differences in the mode of phagocytosis with Fc and C3 receptors in macrophages.Scand. J. Immunol. 1977; 6: 797-807Crossref PubMed Scopus (163) Google Scholar]. Rac and Cdc42 are required for actin and Arp2/3 complex recruitment during FcγR phagocytosis, while Rho controls actin assembly at CR phagosomes [2Caron E. Hall A. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases.Science. 1998; 282: 1717-1721Crossref PubMed Scopus (768) Google Scholar, 3May R.C. Caron E. Hall A. Machesky L.M. Involvement of the Arp2/3 complex in phagocytosis mediated by FcγR or CR3.Nat. Cell Biol. 2000; 2: 246-248Crossref PubMed Scopus (255) Google Scholar]. To better understand the role of Rho in CR phagocytosis, we tested the idea that a known target of Rho, Rho-kinase (ROK), might control phagocytic cup formation and/or engulfment of particles. Inhibitors of ROK (dominant-negative ROK and Y-27632) and of the downstream target of ROK, myosin-II (ML7, BDM, and dominant-negative myosin-II), were used to test this idea. We found that inhibition of the Rho → ROK → myosin-II pathway caused a decreased accumulation of Arp2/3 complex and F-actin around bound particles, which led to a reduction in CR-mediated phagocytic engulfment. FcγR-mediated phagocytosis, in contrast, was independent of Rho or ROK activity and was only dependent on myosin-II for particle internalization, not for actin cup formation. While myosins have been previously implicated in FcγR phagocytosis [4Swanson J.A. Johnson M.T. Beningo K. Post P. Mooseker M. Araki N. A contractile activity that closes phagosomes in macrophages.J. Cell Sci. 1999; 112: 307-316Crossref PubMed Google Scholar, 5Mansfield P.J. Shayman J.A. Boxer L.A. Regulation of polymorphonuclear leukocyte phagocytosis by myosin light chain kinase after activation of mitogen-activated protein kinase.Blood. 2000; 95: 2407-2412Crossref PubMed Google Scholar, 6Diakonova M. Bokoch G. Swanson J.A. Dynamics of cytoskeletal proteins during Fcγ receptor-mediated phagocytosis in macrophages.Mol. Biol. Cell. 2002; 13: 402-411Crossref PubMed Scopus (118) Google Scholar], to our knowledge, this is the first demonstration of a role for myosin-II in CR phagocytosis.