Cofilin-induced structural changes in actin filaments stay local

Actin is a major cytoskeletal protein that plays crucial roles in a number of biological events involving force generation and shape changes. Actin monomers are polymerized into actin filaments, which serve as a core of the actin cytoskeleton together with many associated proteins. Although purified actin can be spontaneously polymerized under physiological conditions in test tubes, assembly and disassembly of actin are spatially and temporally controlled within cells. For example, concerted directional assembly of actin filaments can push membranes and organelles, whereas disassembly of actin filaments contributes to cytoskeletal remodeling and recycling of disassembled actin monomers for a new round of actin polymerization. Therefore, coordinated regulation of actin assembly and disassembly is often required to achieve normal cellular behaviors. Particularly, actin filament disassembly is a challenging task in the cytoplasm. Once actin is polymerized, slow spontaneous dissociation of actin subunits from filaments limits the rate of overall actin turnover. In addition, the cytoplasm generally contains high concentrations of actin monomers that can increase net actin assembly. One of the factors that promote actin filament disassembly is the actin depolymerizing factor (ADF)/cofilin family of proteins, which is expressed in various cell types across eukaryotes and involved in cellular processes that require dynamic rearrangement of the actin cytoskeleton, such as cell migration, cytokinesis, and morphogenesis (1, 2). ADF/cofilin (hereafter referred to as cofilin) promotes actin depolymerization and enhances actin turnover (3⇓–5). Cofilin binds to the side of actin filaments at a 1:1 (cofilin:actin subunit) molar ratio in a cooperative manner such that clusters of cofilin-decorated regions are generated. Then, filament severing occurs frequently at or near boundaries between cofilin-decorated and bare regions on the filament (6, 7). Therefore, cofilin severs actin filaments most efficiently when cofilin binds to filaments at low densities (8). However, the mechanism of … [↵][1]1Email: sono{at}emory.edu. [1]: #xref-corresp-1-1