Sci. Signal., 26 April 2011
Repulsed by OxidizationThe 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 CRMP2s 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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