Functions of cofilin in cell locomotion and invasion

Abstract

Recently, a consensus has emerged that cofilin severing activity can generate free actin filament ends that are accessible for F-actin polymerization and depolymerization without changing the rate of G-actin association and dissociation at either filament end. The structural basis of actin filament severing by cofilin is now better understood. These results have been integrated with recently discovered mechanisms for cofilin activation in migrating cells, which led to new models for cofilin function that provide insights into how cofilin regulation determines the temporal and spatial control of cell behaviour.

NudC regulates actin dynamics and ciliogenesis by stabilizing cofilin 1

“…Actin cytoskeleton participates in many cellular processes, including muscle contraction, cell motility and cell signaling. Cofilin 1 has a pivotal role in actin dynamics by modulating actin polymerization and depolymerization through its severing activity [33][34][35]. Here we find that depletion of NudC causes an accumulation of bundled stress fibers and inhibits cell spreading and lamellipodia formation (Figure 1), resembling the cellular phenotypes induced by cofilin 1 knockdown [29,30,33].…”

The interplay between the proteolytic, invasive, and adhesive domains of invadopodia and their roles in cancer invasion

“…[73][74][75][76] Arp 2/3 actin nucleation is promoted by the severing activity of cofillin. [77][78][79] Additional reports indicate that actin polymerization in invadopodia of certain cancer cells (e.g., MDA-231 breast cancer cell line) can also be induced by specific Diaphanous-related formins, whose cell type specificity, and mode of action and regulation, are still unclear. 80 The actin bundle, thus formed, is further stabilized and mechanically reinforced by cortactin 5 and fascin, 73,81,82 producing a stable "invasive protrusion" that pushes against the ventral cell membrane, promoting its penetration into the ECM.…”

“…36,39,103 (4) Cofilin was shown to promote actin polymerization by its severing activity, which generates free barbed ends that induce the nucleation of actin polymerization by the Arp 2/3 complex. 5,[77][78][79] Cofilin was shown to be important for invadopodia stabilization, most likely due to its interaction with cortactin (see above) and in its absence invadopodia become small and shortlived. 28 Cofilin severing activity is regulated and confined to invadopodia by RhoC and its upstream regulators p190RhoGEF and p190RhoGAP.…”

“…104 RhoC regulation on cofilin is mediated by regulation on cofilin phosphorylation through Rho-associated protein kinase and LIM-domain kinase. 79,104 (5) Fascin is an actin-bundling protein that cross-links actin filaments into a tightly packed bundle. 105,106 In humans, there are three members of the fascin family (1-3), of which fascin 1 is the most widely expressed in tissues.…”

Rho GTPase isoforms in cell motility: Don't fret, we have FRET

“…57 The RhoC biosensor was used to reveal the mechanism by which RhoC contributes to the invasion of tumor cells. Spatial activation of RhoC surrounding the core of invasive protrusions named invadopodia 56 or within regions located behind the leading edge 49 triggers a signaling pathway that phosphorylates cofilin 58 and confines cofilin activity and actin polymerization at the core of invadopodia or to the tip of the leading edge, a localization which is essential for efficient invasion. These activation zones are regulated by the spatial and geometric arrangements of the direct upstream regulators p190RhoGEF and p190RhoGAP.…”