Balancing act: deubiquitinating enzymes in the nervous system

Many pathways important to the nervous system are regulated by the post-translational conjugation of ubiquitin to target proteins. The reversal of ubiquitination, or deubiquitination, is equally critical to neuronal function. By countering protein ubiquitination, deubiquitinating enzymes (DUBs) help control neuronal fate determination, axonal pathfinding and synaptic communication and plasticity. The significance of DUBs to the nervous system is underscored by links to various neurological diseases. Owing to cell type or substrate specificity, certain DUBs might also represent therapeutic targets for neurodegeneration. Here, we review recent findings that have shaped our current understanding of emerging functions for DUBs in the nervous system.