Melanoma cells have been shown to undergo fast amoeboid (leader bleb-based) migration, requiring a single large bleb for migration. In leader blebs, is a rapid flow of cortical actin that drives the cell forward. Using RNAi, we find that co-depleting cofilin-1 and ADF led to a large increase in cortical actin, suggesting that both proteins regulate cortical actin. Furthermore, severing factors can promote contractility through the regulation of actin architecture. However, RNAi of cofilin-1 but not ADF led to a significant decrease in cell stiffness. We found cofilin-1 to be enriched at leader bleb necks, whereas RNAi of cofilin-1 and ADF reduced bleb sizes and the frequency of motile cells. Strikingly, cells without cofilin-1 and ADF had blebs with abnormally long necks. Many of these blebs failed to retract and displayed slow actin turnover. Collectively, our data identifies cofilin-1 and ADF as actin remodeling factors required for fast amoeboid migration.

中文翻译：

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ADF和cofilin-1协作促进皮质肌动蛋白流动和基于先导性起泡的密闭细胞迁移

黑色素瘤细胞已显示出快速的变形虫（基于前导气泡）迁移，仅需一个大气泡即可迁移。在前导泡中，是皮质肌动蛋白的快速流动，推动细胞前进。使用RNAi，我们发现共同消耗cofilin-1和ADF导致皮质肌动蛋白的大量增加，表明这两种蛋白均调节皮质肌动蛋白。此外，切断因子可通过调节肌动蛋白结构来促进收缩。但是，cofilin-1而不是ADF的RNAi导致细胞硬度的显着降低。我们发现cofilin-1在前导颈处富集，而cofilin-1和ADF的RNAi减少了泡的大小和活动细胞的频率。令人惊讶的是，不含cofilin-1和ADF的细胞出现了异常长脖子的起泡。这些气泡中的许多气泡均无法收回，并显示肌动蛋白周转缓慢。