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Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):17821-6. doi: 10.1073/pnas.1413397111. Epub 2014 Dec 2.

Site-specific cation release drives actin filament severing by vertebrate cofilin.

Author information

Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;
Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095; and.
Physics of the Cytoskeleton and Morphogenesis Group, Institut de Recherches en Technologies et Sciences pour le Vivant, Laboratoire de Physiologie Cellulaire Végétale, CNRS, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut National de la Recherche Agronomique, Université Joseph Fourier, Grenoble 38054, France.
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520;


Actin polymerization powers the directed motility of eukaryotic cells. Sustained motility requires rapid filament turnover and subunit recycling. The essential regulatory protein cofilin accelerates network remodeling by severing actin filaments and increasing the concentration of ends available for elongation and subunit exchange. Although cofilin effects on actin filament assembly dynamics have been extensively studied, the molecular mechanism of cofilin-induced filament severing is not understood. Here we demonstrate that actin filament severing by vertebrate cofilin is driven by the linked dissociation of a single cation that controls filament structure and mechanical properties. Vertebrate cofilin only weakly severs Saccharomyces cerevisiae actin filaments lacking this "stiffness cation" unless a stiffness cation-binding site is engineered into the actin molecule. Moreover, vertebrate cofilin rescues the viability of a S. cerevisiae cofilin deletion mutant only when the stiffness cation site is simultaneously introduced into actin, demonstrating that filament severing is the essential function of cofilin in cells. This work reveals that site-specific interactions with cations serve a key regulatory function in actin filament fragmentation and dynamics.


cytoskeleton; electron cryomicroscopy; mechanics; persistence length

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