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

• Published in: Developmental cell Vol. 22; no. 3; pp. 530 - 543
• Main Authors: Wiggan, O'Neil, Shaw, Alisa E., DeLuca, Jennifer G., Bamburg, James R.
• Format: Journal Article
• Language: English
• Published: Cambridge, MA Elsevier Inc 13-03-2012; Cell Press
• Subjects: Actin Depolymerizing Factors - metabolism; Actins - metabolism; Actomyosin - metabolism; Biological and medical sciences; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Fundamental and applied biological sciences. Psychology; HeLa Cells; Humans; Molecular and cellular biology; Myosin Type II - metabolism; Protein Binding; Regulation(control); Myosin ATPase; Enzyme; Actin; Myosin; Development; Hydrolases; Inhibition; Molecular motor
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2011.12.026

The 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.
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► 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
The control of actomyosin assembly in nonmuscle cells remains poorly understood. Wiggan et al. demonstrate that ADF/cofilins from diverse organisms share a conserved activity to inhibit the binding of myosin II to F-actin. They show that regulation of myosin activity by ADF/cofilin is essential for normal cell morphogenesis and division.