Abstract
Cofilin is an actin filament severing protein necessary for fast actin turnover dynamics. Coronin and Aip1 promote cofilin-mediated actin filament disassembly, but the mechanism is somewhat controversial. An early model proposed that the combination of cofilin, coronin, and Aip1 disassembled filaments in bursts. A subsequent study only reported severing. Here, we used EM to show that actin filaments convert directly into globular material. A monomer trap assay also shows that the combination of all three factors produces actin monomers faster than any two factors alone. We show that coronin accelerates the release of Pi from actin filaments and promotes highly cooperative cofilin binding to actin to create long stretches of polymer with a hypertwisted morphology. Aip1 attacks these hypertwisted regions along their sides, disintegrating them into monomers or short oligomers. The results are consistent with a catastrophic mode of disassembly, not enhanced severing alone.
Highlights
The rapid disassembly of actin filaments is necessary for the dramatic shape changes that accompany fundamental cellular processes, such as cell division, endocytosis, and cell motility
We have optimized a protocol with the goal of trapping actin filaments undergoing disassembly to visualize and understand how actin polymer was lost as a function of cofilin, coronin, and Aip1
Our results show that the combination of cofilin, coronin, and Aip1 induces a highly cooperative mode of actin disassembly that is distinct from filament severing
Summary
The rapid disassembly of actin filaments is necessary for the dramatic shape changes that accompany fundamental cellular processes, such as cell division, endocytosis, and cell motility. In the presence of 1.25 mM cofilin, we observed a 30–40% decrease in polymer mass, consistent with the fact that cofilin severs actin filaments and binds ADP-actin monomers that are lost from filament ends with an affinity of 150 nM [6, 41] (Fig. 2A, green line).
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