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

70 Citations (Scopus)

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 (actin(Met(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
StatePublished - Dec 2013

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Actins
Oxidation-Reduction
Semaphorins
sulfoxide
Polymerization
Developmental Biology
Enzymes
Methionine
Cues
Cell Biology
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics. / Hung, Ruei Jiun; Spaeth, Christopher S.; Yesilyurt, Hunkar Gizem; Terman, Jonathan R.

In: Nature Cell Biology, Vol. 15, No. 12, 12.2013, p. 1445-1454.

Research output: Contribution to journalArticle

Hung, RJ, Spaeth, CS, Yesilyurt, HG & Terman, JR 2013, 'SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics.', Nature Cell Biology, vol. 15, no. 12, pp. 1445-1454.
Hung, Ruei Jiun ; Spaeth, Christopher S. ; Yesilyurt, Hunkar Gizem ; Terman, Jonathan R. / SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics. In: Nature Cell Biology. 2013 ; Vol. 15, No. 12. pp. 1445-1454.
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