Working model for twinfilin activities at actin filament barbed ends. Actin filament barbed ends grow by the addition of ATP-actin monomers, which rapidly hydrolyze their bound ATP, producing ADP-Pi–actin subunits. Subsequently, barbed ends are bound by twinfilin alone, capping protein (CP) alone, or twinfilin-capping protein complexes, in each case inhibiting barbed end growth. Twinfilin catalyzes the dissociation of capping protein from barbed ends (Hakala et al., 2019Preprint), leaving twinfilin alone at the barbed end. Twinfilin then induces the depolymerization of ADP-Pi barbed ends, even in the presence of G-actin at concentrations far above the critical concentration for assembly. We postulate that twinfilin achieves these effects using a processive barbed end tracking mechanism, which was directly observed for yeast twinfilin (Johnston et al., 2015). Once twinfilin reaches regions of ADP F-actin, its interactions with the barbed end slow the rate of depolymerization (compared with that of free ADP barbed ends).
