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Dev Cell. 2014 Oct 27;31(2):215-26. doi: 10.1016/j.devcel.2014.09.002.

Cofilin-2 controls actin filament length in muscle sarcomeres.

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Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
Laboratoire de Physiologie Cellulaire et Végétale, Institut de Recherches en Technologies et Sciences pour le Vivant, iRTSV, CNRS/CEA/INRA/UJF, 38054 Grenoble, France.
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. Electronic address:


ADF/cofilins drive cytoskeletal dynamics by promoting the disassembly of "aged" ADP-actin filaments. Mammals express several ADF/cofilin isoforms, but their specific biochemical activities and cellular functions have not been studied in detail. Here, we demonstrate that the muscle-specific isoform cofilin-2 promotes actin filament disassembly in sarcomeres to control the precise length of thin filaments in the contractile apparatus. In contrast to other isoforms, cofilin-2 efficiently binds and disassembles both ADP- and ATP/ADP-Pi-actin filaments. We mapped surface-exposed cofilin-2-specific residues required for ATP-actin binding and propose that these residues function as an "actin nucleotide-state sensor" among ADF/cofilins. The results suggest that cofilin-2 evolved specific biochemical and cellular properties that allow it to control actin dynamics in sarcomeres, where filament pointed ends may contain a mixture of ADP- and ATP/ADP-Pi-actin subunits. Our findings also offer a rationale for why cofilin-2 mutations in humans lead to myopathies.

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