A role for actin arcs in the leading-edge advance of migrating cells

National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Nature Cell Biology (Impact Factor: 19.68). 03/2011; 13(4):371-81. DOI: 10.1038/ncb2205
Source: PubMed


Epithelial cell migration requires coordination of two actin modules at the leading edge: one in the lamellipodium and one in the lamella. How the two modules connect mechanistically to regulate directed edge motion is not understood. Using live-cell imaging and photoactivation approaches, we demonstrate that the actin network of the lamellipodium evolves spatio-temporally into the lamella. This occurs during the retraction phase of edge motion, when myosin II redistributes to the lamellipodial actin and condenses it into an actin arc parallel to the edge. The new actin arc moves rearward, slowing down at focal adhesions in the lamella. We propose that net edge extension occurs by nascent focal adhesions advancing the site at which new actin arcs slow down and form the base of the next protrusion event. The actin arc thereby serves as a structural element underlying the temporal and spatial connection between the lamellipodium and the lamella during directed cell motion.

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    • "To facilitate comparison of frustrated phagocytosis with spreading and migratory processes we analyzed the dynamic spreading morphology using protrusion/retraction activity maps [44] [25] [34] [26] [13]. Similar to spreading fibroblasts [27], activity maps of FP spreading reveal distinct phases of behavior. "
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    • "Because myosin is still present in the central ring after ML7 treatment, it is possible that retraction is still occurring due to myosin-driven contractility of the actin meshwork acting at a distance. However, it has also been reported at least in PtK1 cells that protrusion and retraction cycles still occur after complete myosin II inhibition (Burnette et al., 2011). It seems likely that there are other factors such as actin-depolymerizing proteins (Wilson et al., 2010; Mseka and Cramer, 2011 ) that contribute to retraction in addition to myosin. "
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    Full-text · Article · Apr 2015 · The Journal of Cell Biology
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    • "Thus the contact time and multiplicity of retraction cycles of the lamellipodium at the filopodia adhesions regulates the maturation or disassembly of filopodia adhesions. Cyclic protrusions and retractions of lamellipodia have also been associated with the deposition of circumferential actin filaments that run parallel to the cell edge in various cell types [35], [55], [63] which became efficiently coupled with focal adhesions at the onset of the lamellum right behind the transition zone [64]. Our data now suggest that the circumferential actin filaments become connected with filopodia adhesions behind the lamellipodium-lamellum transition (Fig. 7). "
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    ABSTRACT: While cell-substrate adhesions that form between the protruding edge of a spreading cell and flat surfaces have been studied extensively, processes that regulate the maturation of filopodia adhesions are far less characterized. Since little is known about how the kinetics of formation or disassembly of filopodia adhesions is regulated upon integration into the lamellum, a kinetic analysis of the formation and disassembly of filopodia adhesions was conducted at the leading edge of β3-integrin-EGFP-expressing rat embryonic fibroblasts spreading on fibronectin-coated glass or on soft polyacrylamide gels. Filopodia β3-integrin adhesions matured only if the lamellipodium in their immediate vicinity showed cyclic protrusions and retractions. Filopodia β3-integrin shaft adhesions elongated rapidly when they were overrun by the advancing lamellipodium. Subsequently and once the lamellipodium stopped its advancement at the distal end of the filopodia β3-integrin adhesion, these β3-integrin shaft adhesions started to grow sidewise and colocalize with the newly assembled circumferential actin stress fibers. In contrast, the suppression of the cyclic protrusions and retractions of the lamellipodium by blocking myosin light chain kinase suppressed the growth of filopodia adhesion and resulted in the premature disassembly of filopodia adhesions. The same failure to stabilize those adhesions was found for the advancing lamellipodium that rapidly overran filopodia shaft adhesions without pausing as seen often during fast cell spreading. In turn, plating cells on soft polyacrylamide gels resulted in a reduction of lamellipodia activity, which was partially restored locally by the presence of filopodia adhesions. Thus filopodia adhesions could also mature and be integrated into the lamellum for fibroblasts on soft polyacrylamide substrates.
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