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 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.
Highlights
Cell migration requires tight spatiotemporal control of the filamentous-actin (F-actin) cytoskeleton
Using our previously described approach for cell confinement, which involves placing cells under a slab of PDMS held at a defined height (~3 mm) above cover glass, cancer cells will switch to leader bleb-based migration (LBBM) (Figure 1A and Video 1; Logue et al, 2018)
We set out to determine if actin depolymerizing factor (ADF) and/or cofilin-1 are important for LBBM
Summary
Cell migration requires tight spatiotemporal control of the filamentous-actin (F-actin) cytoskeleton. In amoeboid cells, which migrate using intracellular-driven protrusions of the plasma membrane (PM) or blebs, the mechanisms conferring spatiotemporal control of the F-actin cytoskeleton are not well known. During fast amoeboid migration, cells form a very large and stable bleb. Within these blebs, is a cortical actin network that flows from the bleb tip to the neck, which separates leader blebs from the cell body (Logue et al, 2015; Liu et al, 2015; Ruprecht et al, 2015; Bergert et al, 2015). Because migration plasticity is thought to be a major contributor of metastasis, our aim here is to identify the essential factors required for the rapid cortical actin flow in leader blebs
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