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

eLife

Jeremy S Logue¹  Maria F Ullo¹ 

[1] Department of Regenerative and Cancer Cell Biology, Albany Medical College, Albany, United States;

关键词: cancer;    metastasis;    cell migration;    amoeboid;    cytoskeleton;    actin;    Human;   

DOI  :  10.7554/eLife.67856

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY