• Open Access

Myosin VI and Optineurin Are Required for Polarized EGFR Delivery and Directed Migration

Authors

  • Margarita V. Chibalina,

    1. Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK
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  • Alexei Poliakov,

    1. Division of Developmental Neurobiology, Medical Research Council National Institute for Medical Research, London, NW7 1AA, UK
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  • John Kendrick-Jones,

    1. MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK
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  • Folma Buss

    Corresponding author
    1. Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK
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Folma Buss, fb1@mole.bio.cam.ac.uk

Abstract

The polarized trafficking of membrane proteins into the leading edge of the cell is an integral requirement for cell migration. Myosin VI and its interacting protein optineurin have previously been shown to operate in anterograde trafficking pathways, especially for the polarized delivery of cargo to the basolateral domain in epithelial cells. Here we show that in migratory cells ablation of myosin VI or optineurin inhibits the polarized delivery of the epidermal growth factor receptor (EGFR) into the leading edge and leads to profound defects in lamellipodia formation. Depletion of either myosin VI or optineurin, however, does not impair the overall ability of cells to migrate in a random migration assay, but it dramatically reduces directed migration towards a growth factor stimulus. In summary, we identified a specific role for myosin VI and optineurin in directionally persistent cell migration, which involves the polarized delivery of vesicles containing EGFR into the leading edge of the cell.

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