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

Abstract

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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Figure 1: Retrograde-actin-flow rates change several times over a single edge-protrusion/retraction cycle.
Figure 2: Differential actin-filament turnover during protrusion and retraction.
Figure 3: Actin-arc dynamics at the leading edge.
Figure 4: Myosin II activity condenses the lamellipodium into an actin arc.
Figure 5: Oscillatory edge motion and net edge extension.
Figure 6: Differential slippage of focal adhesions in crawling versus non-crawling cells correlates with new-actin-arc movement.
Figure 7: The advance of the lamella results from an actin-arc treadmill.
Figure 8: Model of the structural dynamics of the actin cytoskeleton underlying edge motion.

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Acknowledgements

We thank the members of the Lippincott-Schwartz Laboratory for helpful comments and suggestions. D.T.B. was supported by a Pharmacology Research Associate Fellowship from NIGMS, NIH during the course of these studies.

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D.T.B., S.M. and J.L-S. designed experiments and wrote the paper. D.T.B. carried out the experiments. D.T.B., S.M. and P.S. analysed the data. M.W.D. contributed new fluorescence probes. R.S. and B.K. contributed expertise in electron microscopy.

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Correspondence to Jennifer Lippincott-Schwartz.

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The authors declare no competing financial interests.

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Burnette, D., Manley, S., Sengupta, P. et al. A role for actin arcs in the leading-edge advance of migrating cells. Nat Cell Biol 13, 371–382 (2011). https://doi.org/10.1038/ncb2205

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