| Popis: |
Physiological levels of ROS are important for several processes in the nervous system, ranging from neuronal precursors proliferation, to axonal guidance and neurotransmission. ROS also support neurite outgrowth and axonal specification, but the mechanisms by which ROS are able to shape neurons remain unknown. We recently showed that NADPH oxidase activity is essential to sustain axon growth. Now, we report that Ca2+ release from the endoplasmic reticulum (ER) is coupled to ROS signaling dependent on NOX2. In this work, we explore the contribution of the link between NOX and RyR-mediated Ca2+ release towards axonal speci fication of rat hippocampal neurons. Using genetic approaches, we find that NOX activation promotes both axonal development and Rac1 activation through a RyR-mediated mechanism, which in turn activates NOX through Rac1, one of the NOX subunits. Collectively, these data suggest a feed-forward mechanism that inte grates both NOX activity and RyR-mediated Ca2+ release to support cellular mechanisms involved in axon development. Finally, we explore the contribution of calcium entry from the extracellular milieu as a triggering factor to promote the concerted functions of NOX and RyR2 during axon specification. |
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