Cofilin-2 controls actin filament length in muscle sarcomeres.

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.

• Authors: Elena Kremneva, Maarit H Makkonen, Aneta Skwarek-Maruszewska, Gergana Gateva, Alphee Michelot, Roberto Dominguez, Pekka Lappalainen
• Journal: Developmental cell (Dev Cell) Vol. 31 Issue 2 Pg. 215-26 (Oct 27 2014) ISSN: 1878-1551 [Electronic] United States
• PMID: 25373779 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• ADP-G-actin
• ATP-G-actin
• Actins
• Cofilin 1
• Cofilin 2
• RNA, Small Interfering
• Adenosine Diphosphate
• Adenosine Triphosphate

Topics

• Actin Cytoskeleton (metabolism, physiology)
• Actins (metabolism)
• Adenosine Diphosphate (analogs & derivatives, metabolism)
• Adenosine Triphosphate (analogs & derivatives, metabolism)
• Amino Acid Sequence
• Animals
• Cells, Cultured
• Cofilin 1 (genetics)
• Cofilin 2 (genetics, metabolism)
• Molecular Sequence Data
• Muscle Contraction (physiology)
• Myocytes, Cardiac (physiology)
• Protein Binding
• RNA Interference
• RNA, Small Interfering
• Rats
• Sarcomeres (physiology)
• Sequence Alignment