title: SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics.
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.
authors.affiliation: Departments of Neuroscience and Pharmacology and Neuroscience Graduate Program, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Ruei-Jiun
authors.initials: RJ
authors.lastname: Hung
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Spaeth
authors.forename: Hunkar Gizem
authors.initials: HG
authors.lastname: Yesilyurt
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Terman
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000502:physiology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D029721:Drosophila Proteins / Q000737:chemistry / Q000502:physiology*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D005260:Female; D008297:Male; D051150:Methionine Sulfoxide Reductases / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D010084:Oxidation-Reduction; D010641:Phenotype; D055503:Protein Multimerization; D015398:Signal Transduction
chemical_list: D000199:Actins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C496247:MICAL protein, Drosophila; D051150:Methionine Sulfoxide Reductases; C495234:SelR protein, Drosophila