85 - Interaction of Peroxiredoxin 2 with Collapsin Response Mediator Protein 2

Abstract

Peroxiredoxins (Prxs) are a family of thiol peroxidases with high reactivity towards hydroperoxides. Their abundance and complex oligomeric structures has led to speculation they are involved in hydrogen peroxide signaling. More specifically, Prxs are proposed to mediate the oxidation of other thiol proteins through a redox-relay involving thiol exchange reactions. In this study Prx2 was immunoprecipitated from cultured cells and specific binding partners identified both before and after the exposure of cells to hydrogen peroxide. Collapsin response mediator protein 2 (CRMP2) was identified as an interaction partner, and proximity ligation assays confirmed the two proteins were co-localised in situ. CRMP2 is a tubulin-binding protein that regulates microtubule stability. Oxidation and phosphorylation of CRMP2 promote microtubule collapse. Exposure of cells to hydrogen peroxide caused simultaneous oxidation of both Prx2 and CRMP2, even though purified CRMP2 was resistant to oxidation. Knockdown of Prx2 expression resulted in decreased CRMP2 oxidation, supporting a redox-relay in which Prx2 facilitates the oxidation and regulation of CRMP2. Transient oxidation of CRMP2 is proposed to assist in cytoskeletal collapse of neuronal growth cones in response to extracellular guidance cues. Disruption of the Prx2/CRMP2 redox relay may protect CRMP2 from oxidation under conditions of sustained oxidative stress.