Research ArticleNeuroscience

Thioredoxin Mediates Oxidation-Dependent Phosphorylation of CRMP2 and Growth Cone Collapse

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Science Signaling  26 Apr 2011:
Vol. 4, Issue 170, pp. ra26
DOI: 10.1126/scisignal.2001127

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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.

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