Long-Range and Directional Allostery of Actin Filaments Plays Important Roles in Various Cellular Activities

Figures

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  Figure 1. Possible contribution of allosteric interaction between actin-binding proteins (ABPs) and actin filaments to the formation and functions of actin-based machineries, including stress fiber, lamellipodium, and filopodium. Green filaments indicate actin filaments along which cooperative structural changes are evoked by myosin II. Blue filaments in lamellipodium and filopodia are polymerized by formin bound to the barbed end near the cell membrane [78]. Formin would induce a cooperative structural change, but those structural changes do not reach all the way to the pointed ends of filaments (gray sections of the filaments). The binding of cofilin to the gray regions induced another type of structural change (magenta filaments), so that the actin filaments are depolymerized in regions deeper inside the cell. The detailed mechanism driven by cooperative structural changes in actin filaments constituting the stress fibers, lamellipodia and filopodia will be explained in the following sections.

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  Figure 2. Stress fiber composed of tropomyosin, α-actinin, and myosin II, and the proposed mechanism for how cofilin is excluded. The binding of myosin II (and probably tropomyosin and α-actinin) to actin filaments induces a cooperative structural change of filaments accompanied by untwisting of the helix (green filaments). In addition, stress fibers are also tensed by the movement of myosin II. The untwisting and tension of the actin filaments presumably involve constructing a stress fiber that repels cofilin.

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  Figure 3. Severing of formin-bound actin filament by cofilin in lamellipodia. Formin bound to the barbed end of an actin filament induces untwisting of the filament (blue), but the effect does not reach the pointed end of filaments (grey) deeper inside the cells because the untwisting is presumably blocked at the branching point where ARP2/3 complex is connected. Cofilin binds to the grey section of the filament unaffected by formin and causes cooperative structural changes with supertwisting of filaments (magenta). Cofilin clusters grow in the magenta area, and the actin filament is severed.

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  Figure 4. Extension and stabilization of filopodia. Similar to lamellipodia, in filopodia, formin binds to the barbed end of actin filaments and untwists the filaments. Since fascin can bind to actin filaments regardless of this structural change, filaments are bundled in filopodia. The formin-induced untwisting is presumably blocked and not propagated to the pointed-end of filaments by the immobilization by fascin. Cofilin cannot bind not only to the untwisted segments near the tip of filopodia, but also to the bundled sections, since those bundled sections cannot be supertwisted.