Myosin VI and optineurin are required for polarized EGFR delivery and directed migration.
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.
Chibalina
Margarita V
MV
Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK.
Poliakov
Alexei
A
Kendrick-Jones
John
J
Buss
Folma
F
D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002465:Cell Movement; D016764:Cell Polarity; D004705:Endocytosis; D066246:ErbB Receptors / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins; D018995:Myosin Heavy Chains / Q000378:metabolism*; D035582:Transcription Factor TFIIIA / Q000378:metabolism*
D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C409460:OPTN protein, human; D035582:Transcription Factor TFIIIA; C089785:myosin VI; D066246:ErbB Receptors; D018995:Myosin Heavy Chains