A dual need for myosin in wounds

Abstract

Myosin takes both the high road and the low road to close wounds, as revealed by Tamada et al. on page 27. The motor is found in a high contractile actin ring and in bottom-dwelling membrane protrusions. Figure 1 A ring of myosin (red) at apical junctions (green) on the wound (*) face tugs cells inwards while basal myosin spurs on cell migration. Wound closure requires a cable of actin and myosin in the cells that border the wound. The contraction of this cable draws these border cells together to fill in the hole. In flies, however, border cells seem rather to migrate inward, dragging the cells behind them forward into the wound. Now, new videos suggest that both migration and ring contraction help to close wounds in mammalian epithelia. The videos examine myosin localization from a unique perspective. After creating a circular injury site in an epithelial sheet, the authors imaged the wound-adjacent cells from a side view as healing progressed. They saw actin and myosin accumulate at apical tight junctions. Viewed from above, the accumulation formed a ring around the wound. Myosin-mediated contraction of the ring was required to close the wound fully. The contractile shortening of the actomyosin ring stretched the cells thin, pulling the apical membrane down and inwards into the wound. During stretching, apical myosin moved together with a junctional protein called ZO-1, and both eventually met with the basal membrane. The authors suggest that, given this close association, tight junction proteins might provide a structural scaffold for ring assembly. The side view revealed that the apical ring only formed on the side of the cell facing the lost neighbor. Group leader Michael Sheetz speculates that a mechanical signal, such as the loss of tension at those junctions, is the initiator of myosin assembly. Tension loss might be noted by p130cas, which his group recently showed to be a mechanosensor. In addition to the top ring, a basal accumulation of myosin was also seen, near lamellopodial protrusions that moved out into the wound, as seen in flies. Without this basal myosin activity, the cells formed spikey filopodium-like extensions instead of lamellipodia. Spikes were only able to close the wound partially. Mammalian cells thus seem to require two myosin rings for full closure.