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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.

Author information

1
Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland.
2
Laboratoire de Physiologie Cellulaire et Végétale, Institut de Recherches en Technologies et Sciences pour le Vivant, iRTSV, CNRS/CEA/INRA/UJF, 38054 Grenoble, France.
3
Department of Physiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Institute of Biotechnology, University of Helsinki, P.O. Box 56, 00014 Helsinki, Finland. Electronic address: pekka.lappalainen@helsinki.fi.

Abstract

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.

PMID:
25373779
PMCID:
PMC4223631
DOI:
10.1016/j.devcel.2014.09.002
[Indexed for MEDLINE]
Free PMC Article

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