Background: The initial stages of phagocytosis and cell motility resemble each other. The extension of a pseudopod at the leading edge of a migratory cell and the formation of a phagocytic cup are actin dependent, and each rely on the plasma membrane adhering to a surface during dynamic extension. Results: A myosin VII null mutant exhibited a drastic loss of adhesion to particles, consistent with the extent of an observed decrease in particle uptake. Additionally, cell-cell adhesion and the adhesion of the leading edge to the substratum during cell migration were defective in the myosin VII null cells. GFP-myosin VII rescued the phagocytosis defect of the null mutant and was distributed in the cytosol and recruited to the cortical cytoskeleton, where it appeared to be enriched at the tips of filopods. It was also localized to phagocytic cups, but only during the initial stages of particle engulfment. During migration, GFP-myosin VII is found at the leading edge of the cell. Conclusions: Myosin VII plays an important role in mediating the initial binding of cells to substrata, a novel role for an unconventional myosin.
Bibliographical noteFunding Information:
The authors would like to thank Dr. Scott Kuo for his design of the microscopy chamber and Drs. Cathy Chia and Pierre Cosson for supplying antibodies. We would also like to thank Dr. Gaku Ashiba for his helpful discussions throughout this project, Drs. Tom Hays and Pamela Taylor for their comments on the manuscript, and members of the Soll laboratory for their help with the 3D analysis. This work was supported by grants from the National Science Foundation to M.A.T., from the Deutsche Forschungsgemeinschaft to G.G., and from the National Institutes of Health to D.R.S. The W.M. Keck Dynamic Image Analysis Facility at the University of Iowa is funded by the W.M. Keck Foundation. R.I.T. is supported by a long-term fellowship from the Human Frontier Science Project.