ADF and cofilin-1 collaborate to promote cortical actin flow and the leader bleb-based migration of confined cells

• Main Authors: Maria F Ullo, Jeremy S Logue
• Format: Article
• Language: English
• Published: eLife Sciences Publications Ltd 2021-06-01
• Series: eLife
• Subjects: cancer; metastasis; cell migration; amoeboid; cytoskeleton; actin
• Online Access: https://elifesciences.org/articles/67856

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 actin depolymerizing factor (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.