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SelR reverses Mical-mediated oxidation of actin to regulate F-actin dynamics

Nature Cell Biology volume 15, pages 14451454 (2013) | Download Citation

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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.

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Acknowledgements

We thank C. Cowan, E. Kavalali, H. Kramer, C. Pak, E. Reisler and M. Rosen for comments and FlyBase, J. Yoon (UT Southwestern, USA), H. Aberle (University of Münster, Germany), Kyoto Stock Center, Vienna Drosophila RNAi Center and the Bloomington Stock Center for reagents. Mass spectrometry was performed by Y. Li (UT Southwestern Protein Chemistry Technology Center). Supported by Cancer Prevention Research Institute of Texas (CPRIT) predoctoral (R-J.H.), NIDA T-32-DA7290 postdoctoral (C.S.S.) and NIH (NS073968; MH085923) and Welch Foundation (I-1749) (J.R.T.) grants.

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  1. Departments of Neuroscience and Pharmacology and Neuroscience Graduate Program, The University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA

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

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Contributions

R-J.H., C.S.S., H.G.Y. and J.R.T. designed/performed experiments and analysed data, R-J.H., C.S.S. and J.R.T. prepared the manuscript, R-J.H. wrote the paper, and C.S.S. and J.R.T. assisted in the writing of the paper.

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The authors declare no competing financial interests.

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Correspondence to Jonathan R. Terman.

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https://doi.org/10.1038/ncb2871

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