The nervous system coordinates many aspects of body function such as learning, memory, behaviour and locomotion. Therefore, it must develop and maintain an intricate network of differentiated neuronal cells, which communicate efficiently with each other and with non-neuronal target cells. Unlike most somatic cells, differentiated neurons are post-mitotic and characterized by a highly polarized morphology that determines the flow of information. Among other post-translational modifications, the ubiquitination of specific protein substrates was recently shown to have a crucial role in the regulation of neuronal development and differentiation. Here, we review recent findings that illustrate the mechanisms that mediate the temporal and spatial control of neuronal protein turnover by the ubiquitin-proteasome system (UPS), which is crucial for the development and function of the nervous system.
