A keratocyte with actin filaments labeled in red by fluorescent phalloidin, and cofilin labeled in green with a fluorescent antibody. Although the dense actin meshwork reaches all the way through the lamellipodium, cofilin is not found at the very leading edge. (B) Close-up view of the region marked with the white rectangle in (A). The actin filaments closest to the leading edge, which are also the ones that have formed most recently and that are most likely to contain ATP-actin (rather than ADP-actin), are generally not associated with cofilin. (From T. Svitkina and G. Borisy,
J.
Cell Biol. 145:1009–1026, 1999. With permission from the authors.)
Figure 16–80 A model for protrusion of the actin meshwork at the leading edge. Two time points during advance of the lamellipodium are illustrated, with newly assembled structures at the later time point shown in a lighter color. Nucleation is mediated by the Arp 2/3 complex at the front. Newly nucleated actin filaments are attached to the sides of preexisting filaments, primarily at a 70° angle. Filaments elongate, pushing the plasma membrane forward because of some sort of anchorage of the array behind. At a steady rate, actin filament plus ends become capped. After newly polymerized actin subunits hydrolyze their bound ATP in the filament lattice, the filaments become susceptible to depolymerization by cofilin. This cycle causes a spatial separation between net filament assembly at the front and net filament disassembly at the rear, so that the actin filament network as a whole can move forward, even though the individual filaments within it remain stationary with respect to the substratum. Not all of the actin disassembles, however, and actin at the rear of the lamellipodium contributes to subsequent steps of migration together with myosin.
Figure 16–81 Contribution of myosin II to polarized cell motility.