Synergistic assembly, disassembly, and protection of complex forms of bundled F-actin

Actin's transition from monomers (G-actin) to polymers (F-actin) and then into bundled and branched networks underlies many cellular and system functions. Yet, how these networks are dynamically assembled and disassembled is incompletely understood-including why F-actin is often simultaneously and redundantly bundled by different proteins. Here, we focus on fascin and espin, two bundlers that often coexist and robustly bundle F-actin. We find that they synergistically bundle F-actin compared to equal amounts of each one alone. However, we show that bundles containing these two proteins are robustly destabilized by a synergism between Mical and cofilin, indicating mechanisms of how complex bundles are disassembled and remodeled. Yet, our results also reveal that together fascin and espin protect F-actin from this disassembly more effectively than each one alone-including to regulate F-actin disassembly and cellular remodeling in vivo. These findings reveal mechanisms for assembling and disassembling complex networks of bundled F-actin, including a synergism between different bundlers and disassemblers in these processes.