Spatial organization of ubiquitin ligase pathways orchestrates neuronal connectivity

Recent studies have revealed that E3 ubiquitin ligases have essential functions in the establishment of neuronal circuits. Strikingly, a common emerging theme in these studies is that spatial organization of E3 ubiquitin ligases plays a critical role in the control of neuronal morphology and connectivity. E3 ubiquitin ligases localize to the nucleus, centrosome, Golgi apparatus, axon and dendrite cytoskeleton, and synapses in neurons. Localization of ubiquitin ligases within distinct subcellular compartments may facilitate neuronal responses to extrinsic cues and the ubiquitination of local substrates. Here, we review the functions of neuronal E3 ubiquitin ligases at distinct subcellular locales and explore how they regulate neuronal morphology and function in the nervous system.