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Sci. Signal., 26 April 2011
Vol. 4, Issue 170, p. ra26
[DOI: 10.1126/scisignal.2001127]


Editor's Summary

Repulsed by Oxidization
The axonal guidance molecule Semaphorin3A (Sema3A) stimulates the phosphorylation of collapsin response mediator protein 2 (CRMP2), acting as an inhibitory signal to induce growth cone collapse. Here, Morinaka et al. unravel the underlying mechanisms that lead to CRMP2 phosphorylation by glycogen synthase kinase–3 (GSK-3), identifying a redox step in what appeared to be a classical phosphorylation event. They showed that Sema3A stimulated the production of H2O2 by the flavoprotein MICAL (molecule interacting with CasL), leading to CRMP2 oxidation and thereby its formation of a disulfide-linked homodimer. CRMP2 oxidation also led to formation of a transient complex with the oxidoreductase thioredoxin, an interaction that promoted CRMP2’s phosphorylation by GSK-3 and thereby growth cone collapse.

Citation: A. Morinaka, M. Yamada, R. Itofusa, Y. Funato, Y. Yoshimura, F. Nakamura, T. Yoshimura, K. Kaibuchi, Y. Goshima, M. Hoshino, H. Kamiguchi, H. Miki, Thioredoxin Mediates Oxidation-Dependent Phosphorylation of CRMP2 and Growth Cone Collapse. Sci. Signal. 4, ra26 (2011).

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Identification of a Dithiol-disulfide Switch in Collapsin Response Mediator Protein 2 (CRMP2) That Is Toggled in a Model of Neuronal Differentiation.
M. Gellert, S. Venz, J. Mitlohner, C. Cott, E.-M. Hanschmann, and C. H. Lillig (2013)
J. Biol. Chem. 288, 35117-35125
   Abstract »    Full Text »    PDF »
CRMP2 Protein SUMOylation Modulates NaV1.7 Channel Trafficking.
E. T. Dustrude, S. M. Wilson, W. Ju, Y. Xiao, and R. Khanna (2013)
J. Biol. Chem. 288, 24316-24331
   Abstract »    Full Text »    PDF »
Thioredoxin-related Protein 32 (TRP32) Specifically Reduces Oxidized Phosphatase of Regenerating Liver (PRL).
T. Ishii, Y. Funato, and H. Miki (2013)
J. Biol. Chem. 288, 7263-7270
   Abstract »    Full Text »    PDF »
Regulation of intracellular signalling through cysteine oxidation by reactive oxygen species.
H. Miki and Y. Funato (2012)
J. Biochem. 151, 255-261
   Abstract »    Full Text »    PDF »
Direct Redox Regulation of F-Actin Assembly and Disassembly by Mical.
R.-J. Hung, C. W. Pak, and J. R. Terman (2011)
Science 334, 1710-1713
   Abstract »    Full Text »    PDF »

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