Cambridge Institute for Medical Research, Department of Clinical Biochemistry, University of Cambridge, Wellcome Trust/MRC Building, Hills Road, Cambridge, CB2 0XY, UK.
Traffic. 2010 Oct;11(10):1290-303. doi: 10.1111/j.1600-0854.2010.01101.x.
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.
膜蛋白向细胞前缘的极化运输是细胞迁移的一个基本要求。肌球蛋白 VI 和它的相互作用蛋白视神经病变蛋白先前被证明在顺行运输途径中起作用，特别是对于货物向上皮细胞的基底外侧区域的极化输送。在这里，我们表明，在迁移细胞中，肌球蛋白 VI 或视神经病变蛋白的消融抑制了表皮生长因子受体 (EGFR) 向前缘的极化输送，并导致片状伪足形成的严重缺陷。然而，肌球蛋白 VI 或视神经病变蛋白的耗竭并不损害细胞在随机迁移测定中整体迁移的能力，但它显著降低了细胞向生长因子刺激的定向迁移。总之，我们确定了肌球蛋白 VI 和视神经病变蛋白在定向持久细胞迁移中的特定作用，该作用涉及含有 EGFR 的囊泡向细胞前缘的极化输送。
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