TY - JOUR TI - ADF and cofilin-1 collaborate to promote cortical actin flow and the leader bleb-based migration of confined cells AU - Ullo, Maria F AU - Logue, Jeremy S A2 - Michelot, Alphee A2 - Akhmanova, Anna A2 - Michelot, Alphee VL - 10 PY - 2021 DA - 2021/06/25 SP - e67856 C1 - eLife 2021;10:e67856 DO - 10.7554/eLife.67856 UR - https://doi.org/10.7554/eLife.67856 AB - 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. KW - cancer KW - metastasis KW - cell migration KW - amoeboid KW - cytoskeleton KW - actin JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -