Rho-kinase and myosin-II control phagocytic cup formation during CR, but not FcgammaR, phagocytosis

Curr Biol. 2002 Aug 20;12(16):1413-18. doi: 10.1016/s0960-9822(02)01069-2.

Abstract

Phagocytosis through Fcgamma receptor (FcgammaR) or complement receptor 3 (CR) requires Arp2/3 complex-mediated actin polymerization, although each receptor uses a distinct signaling pathway. Rac and Cdc42 are required for actin and Arp2/3 complex recruitment during FcgammaR phagocytosis, while Rho controls actin assembly at CR phagosomes. 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. FcgammaR-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 FcgammaR phagocytosis, to our knowledge, this is the first demonstration of a role for myosin-II in CR phagocytosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Cell Line
  • Cytoskeletal Proteins / metabolism
  • Enzyme Inhibitors / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • Macrophage-1 Antigen / metabolism*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Myosin Type II / metabolism*
  • Myosin-Light-Chain Kinase / antagonists & inhibitors
  • Myosin-Light-Chain Kinase / metabolism
  • Phagocytosis / physiology*
  • Phagosomes / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptors, IgG / metabolism*
  • rho-Associated Kinases

Substances

  • Actins
  • Cytoskeletal Proteins
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Macrophage-1 Antigen
  • Receptors, IgG
  • Protein-Serine-Threonine Kinases
  • rho-Associated Kinases
  • Myosin-Light-Chain Kinase
  • Myosin Type II