Journal
DEVELOPMENTAL CELL
Volume 31, Issue 2, Pages 215-226Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2014.09.002
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Funding
- Academy of Finland
- Finnish Foundation for Cardiovascular Research
- GPBM graduate program
- VGSB graduate program
- NIH [R01 GM073791]
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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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