PT  - JOURNAL ARTICLE
AU  - Maria F. Ullo
AU  - Jeremy S. Logue
TI  - ADF and cofilin-1 collaborate to promote cortical actin flow and the leader bleb-based migration of confined cells
AID  - 10.1101/2021.01.11.426289
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.11.426289
4099  - http://biorxiv.org/content/early/2021/02/24/2021.01.11.426289.short
4100  - http://biorxiv.org/content/early/2021/02/24/2021.01.11.426289.full
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 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.Competing Interest StatementThe authors have declared no competing interest.