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

34 Citations (Scopus)

Abstract

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
Volume18
Issue number8
DOIs
StatePublished - Aug 1 2016

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Actin Depolymerizing Factors
Oxidation-Reduction
Actins
Destrin
Semaphorins
Actin Cytoskeleton

ASJC Scopus subject areas

  • Medicine(all)
  • Cell Biology

Cite this

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

F-actin dismantling through a redox-driven synergy between Mical and cofilin. / Grintsevich, Elena E.; Yesilyurt, Hunkar Gizem; Rich, Shannon K.; Hung, Ruei Jiun; Terman, Jonathan R.; Reisler, Emil.

In: Nature Cell Biology, Vol. 18, No. 8, 01.08.2016, p. 876-885.

Research output: Contribution to journalArticle

Grintsevich, EE, Yesilyurt, HG, Rich, SK, Hung, RJ, Terman, JR & Reisler, E 2016, 'F-actin dismantling through a redox-driven synergy between Mical and cofilin', Nature Cell Biology, vol. 18, no. 8, pp. 876-885. https://doi.org/10.1038/ncb3390
Grintsevich, Elena E. ; Yesilyurt, Hunkar Gizem ; Rich, Shannon K. ; Hung, Ruei Jiun ; Terman, Jonathan R. ; Reisler, Emil. / F-actin dismantling through a redox-driven synergy between Mical and cofilin. In: Nature Cell Biology. 2016 ; Vol. 18, No. 8. pp. 876-885.
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