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Myosin X is a downstream effector of PI(3)K during phagocytosis

Nature Cell Biology volume 4, pages 469–477 (2002)Cite this article

Abstract

Phagocytosis is a phosphatidylinositol-3-OH-kinase (PI(3)K)-dependent process in macrophages. We identified Myo10 (Myosin-X), an unconventional myosin with pleckstrin homology (PH) domains, as a potential downstream target of PI(3)K. Myo10 was recruited to phagocytic cups in a wortmannin-sensitive manner. Expression of a truncation construct of Myo10 (Myo10 tail) in a macrophage cell line or cytosolic loading of anti-Myo10 antibodies in bovine alveolar macrophages inhibited phagocytosis. In contrast, expression of a Myo10 tail construct containing a point mutation in one of its PH domains failed to inhibit phagocytosis. Expression of Myo10 tail inhibited spreading, but not adhesion, on IgG-coated substrates, consistent with a function for Myo10 in pseudopod extension. We propose that Myo10 provides a molecular link between PI(3)K and pseudopod extension during phagocytosis.

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Figure 1: Myo10 is present in macrophages.
Figure 2: Myo10 is localized to phagocytic cups.
Figure 3: Myo10 is recruited to phagocytic cups in a PI(3)K-dependent manner.
Figure 4: Intact Myo10 function is required for FcγR-mediated phagocytosis.
Figure 5: Myo10 tail is present in phagocytic cups.
Figure 6: Expression of Myo10 tail does not inhibit Rac1- or Cdc42-mediated actin assembly.
Figure 7: Inhibition of phagocytosis by Myo10 tail expression is dependent on particle size.
Figure 8: Expression of Myo10 tail inhibits spreading, but not adhesion, of macrophages on IgG-coated substrates.

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Acknowledgements

This work was supported by National Institutes of Health grants HL54164 to S.G., K01 AR02158 to D.C. and DC03299 to R.E.C.

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Authors and Affiliations

  1. Department of Medicine, Columbia University, 630 West 168th Street, New York, 10032, NY, USA

    Dianne Cox, John O. Chinegwundoh, Benjamin M. Dale & Steven Greenberg

  2. Department of Cell and Molecular Physiology, UNC-Chapel Hill, Chapel Hill, 27599, NC, USA

    Steven Greenberg

  3. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine Yeshiva University, Bronx, New York, 10461, NY, USA

    Jonathan S. Berg & Richard E. Cheney

  4. Department of Pharmacology, Columbia University, 630 West 168th Street, New York, 10032, NY, USA

    Michael Cammer

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Correspondence to Steven Greenberg.

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Supplementary figures

Figure 1. Expression of Myo10 tail does not inhibit transferrin receptor recruitment to phagocytic cups. (PDF 332 kb)

Figure 2. Expression of Myo10 tail does not inhibit macropinocytosis.

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Cox, D., Berg, J., Cammer, M. et al. Myosin X is a downstream effector of PI(3)K during phagocytosis. Nat Cell Biol 4, 469–477 (2002). https://doi.org/10.1038/ncb805

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