Wnt proteins are emerging key regulators of the plasticity and functions of adult brains. However, the mechanisms\r\nby which the expression of Wnt proteins is regulated in neurons are unclear. Using cortical primary cultures, we\r\nshow here that activation of NMDA receptors (NMDARs) induces rapid Wnt5a protein synthesis and secretion. This\r\nNMDAR-regulated Wnt5a synthesis does not require transcription and is a result of activity-dependent translation.\r\nWe also show that NMDAR-regulated Wnt5a translation depends on MAPK signaling but not mTOR signaling. Our\r\nfindings suggest that the synaptic activity of CNS neurons activates NMDARs, which in turn stimulate translation\r\nfrom stored Wnt5a mRNA via the MAPK signaling pathway
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