ADF/Cofilin Regulates Actomyosin Assembly through Competitive Inhibition of Myosin II Binding to F-Actin

SummaryThe contractile actin cortex is important for diverse fundamental cell processes, but little is known about how the assembly of F-actin and myosin II motors is regulated. We report that depletion of actin depolymerizing factor (ADF)/cofilin proteins in human cells causes increased contractile cortical actomyosin assembly. Remarkably, our data reveal that the major cellular defects resulting from ADF/cofilin depletion, including cortical F-actin accumulation, were largely due to excessive myosin II activity. We identify that ADF/cofilins from unicellular organisms to humans share a conserved activity to inhibit myosin II binding to F-actin, indicating a mechanistic rationale for our cellular results. Our study establishes an essential requirement for ADF/cofilin proteins in the control of normal cortical contractility and in processes such as mitotic karyokinesis. We propose that ADF/cofilin proteins are necessary for controlling actomyosin assembly and intracellular contractile force generation, a function of equal physiological importance to their established roles in mediating F-actin turnover.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (99 K)Download as PowerPoint slideHighlights► Cofilin regulates myosin II function through competitive binding to F-actin ► Cofilin modulates actin filament tension and contractility ► Cofilin controls normal cortical stability, membrane dynamics, and karyokinesis ► Excessive myosin activity drives major cellular defects after cofilin depletion