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

Abstract
Data availability
Article and author information
Metrics

Abstract

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.

Data availability

Source data files for Figures 1, 2, and 5 have been provided.

Article and author information

Author details

Maria F Ullo

Regenerative and Cancer Cell Biology, Albany Medical College, Albany, United States

Competing interests
The authors declare that no competing interests exist.
Jeremy S Logue

Regenerative and Cancer Cell Biology, Albany Medical College, Albany, United States

For correspondence
loguej@mail.amc.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-5274-2052

Funding

Melanoma Research Alliance (688232)

Maria F Ullo
Jeremy S Logue

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Copyright

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.