Translational regulation of the expression of the ubiquitin E3 ligase Nedd4–1 by mTORC1-dependent signaling

We found recently that mTORC1 regulates the biosynthesis of the ubiquitin E3 ligase Nedd4–1, but not the close homolog Nedd4–2. This regulatory process plays a key role in promoting neurite growth in neurons of the mammalian central nervous system. The molecular mechanism underlying this rather specific regulation likely involves a pyrimidine-rich sequence stretch near the putative transcriptional start site within the 5′ untranslated region of the Nedd4–1 mRNA, which may play a crucial role in directing the assembly of the protein translation machinery. We postulate that the Nedd4–1 mRNA is a major target of the local translation machinery within neurons that can be translated in a spatially and temporally controlled manner in response to various stimuli. Based on this model, neuronal Nedd4–1 may not only be involved in the regulation of neurite growth but also in axon guidance, spine formation, and synaptic plasticity.