Abstract
Wnt proteins are emerging key regulators of the plasticity and functions of adult brains. However, the mechanisms by which the expression of Wnt proteins is regulated in neurons are unclear. Using cortical primary cultures, we show here that activation of NMDA receptors (NMDARs) induces rapid Wnt5a protein synthesis and secretion. This NMDAR-regulated Wnt5a synthesis does not require transcription and is a result of activity-dependent translation. We also show that NMDAR-regulated Wnt5a translation depends on MAPK signaling but not mTOR signaling. Our findings suggest that the synaptic activity of CNS neurons activates NMDARs, which in turn stimulate translation from stored Wnt5a mRNA via the MAPK signaling pathway.
Highlights
Wnts are secreted glycoproteins that regulate cell morphologies and behaviors by stimulating complicate intracellular signaling cascades
These results indicate that NMDA receptors (NMDARs) activation is sufficient to stimulate Wnt5a up-regulation
In this study, we found that NMDAR activation rapidly increases the synthesis of Wnt5a protein
Summary
Wnts are secreted glycoproteins that regulate cell morphologies and behaviors by stimulating complicate intracellular signaling cascades. Previous work has established that Wnt signaling controls many oncogenic and developmental processes [1,2]. More recent studies have revealed that Wnt signaling is critically involved in key processes of the formation and plasticity of the nervous system, including neurogenesis [3], axon guidance [4], dendritic development [5], synaptic differentiation [6] and plasticity [7,8]. Wnt5a is member of the Wnt protein family and plays important roles in outgrowth, guidance and branching of axons [17,18]; genesis of dopaminergic neurons [19]; and formation and plasticity of both excitatory and inhibitory synapses [20,21,22].
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