F-actin dismantling through a redox-driven synergy between Mical and cofilin

Elena E. Grintsevich, Hunkar Gizem Yesilyurt, Shannon K. Rich, Ruei Jiun Hung, Jonathan R. Terman, Emil Reisler

Research output: Contribution to journalArticle

41 Scopus citations


Numerous cellular functions depend on actin filament (F-actin) disassembly. The best-characterized disassembly proteins, the ADF (actin-depolymerizing factor)/cofilins (encoded by the twinstar gene in Drosophila), sever filaments and recycle monomers to promote actin assembly. Cofilin is also a relatively weak actin disassembler, posing questions about mechanisms of cellular F-actin destabilization. Here we uncover a key link to targeted F-actin disassembly by finding that F-actin is efficiently dismantled through a post-translational-mediated synergism between cofilin and the actin-oxidizing enzyme Mical. We find that Mical-mediated oxidation of actin improves cofilin binding to filaments, where their combined effect dramatically accelerates F-actin disassembly compared with either effector alone. This synergism is also necessary and sufficient for F-actin disassembly in vivo, magnifying the effects of both Mical and cofilin on cellular remodelling, axon guidance and Semaphorin-Plexin repulsion. Mical and cofilin, therefore, form a redox-dependent synergistic pair that promotes F-actin instability by rapidly dismantling F-actin and generating post-translationally modified actin that has altered assembly properties.

Original languageEnglish (US)
Pages (from-to)876-885
Number of pages10
JournalNature cell biology
Issue number8
StatePublished - Aug 1 2016

ASJC Scopus subject areas

  • Cell Biology

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    Grintsevich, E. E., Yesilyurt, H. G., Rich, S. K., Hung, R. J., Terman, J. R., & Reisler, E. (2016). F-actin dismantling through a redox-driven synergy between Mical and cofilin. Nature cell biology, 18(8), 876-885. https://doi.org/10.1038/ncb3390