Selr Reverses Mical-Mediated Oxidation of Actin to Regulate F-Actin Dynamics

Ruei Jiun Hung, Christopher S. Spaeth, Hunkar Gizem Yesilyurt, Jonathan R. Terman

Research output: Contribution to journalArticle

77 Scopus citations

Abstract

Actin’s polymerization properties are markedly altered by oxidation of its conserved Met 44 residue. Mediating this effect is a specific oxidation–reduction (redox) enzyme, Mical, that works with Semaphorin repulsive guidance cues and selectively oxidizes Met 44. We now find that this actin-regulatory process is reversible. Employing a genetic approach, we identified a specific methionine sulfoxide reductase (MsrB) enzyme SelR that opposes Mical redox activity and Semaphorin–Plexin repulsion to direct multiple actin-dependent cellular behaviours in vivo. SelR specifically catalyses the reduction of the R isomer of methionine sulfoxide (methionine-R-sulfoxide) to methionine, and we found that SelR directly reduced Mical-oxidized actin, restoring its normal polymerization properties. These results indicate that Mical oxidizes actin stereospecifically to generate actin Met-44-R-sulfoxide (actinMet(R)O−44), and also implicate the interconversion of specific Met/Met(R)O residues as a precise means to modulate protein function. Our results therefore uncover a specific reversible redox actin regulatory system that controls cell and developmental biology.

Original languageEnglish (US)
Pages (from-to)1445-1454
Number of pages10
JournalNature Cell Biology
Volume15
Issue number12
DOIs
StatePublished - Dec 2013

    Fingerprint

ASJC Scopus subject areas

  • Cell Biology

Cite this