title: Translational regulation of the expression of the ubiquitin E3 ligase Nedd4-1 by mTORC1-dependent signaling.
abstract: 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.
authors.affiliation: Department of Molecular Neurobiology; Max Planck Institute of Experimental Medicine ; Göttingen, Germany.
authors.forename: Hung-En
authors.initials: HE
authors.lastname: Hsia
authors.affiliation: Department of Molecular Neurobiology; Max Planck Institute of Experimental Medicine ; Göttingen, Germany.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawabe
keywords: Nedd4–1; mTORC1; translation