This could provide proteins for in situ repair of ribosomes, or even more interestingly could provide onsite “tuning” of translation (Lee et al., 2013). One of the most exciting clinically relevant findings

to emerge from recent work is the link between dysregulated synaptic protein synthesis and neurological disorders (Bear CX-5461 in vitro et al., 2008, Darnell and Klann, 2013 and Liu-Yesucevitz et al., 2011). Mouse models of neurodevelopmental disorders such as autism spectrum disorder (ASD) show significant improvement on treatment with reagents that target the protein-synthesis pathway (Bear et al., 2008, Darnell and Klann, 2013, Gkogkas et al., 2013 and Santini et al., 2013), opening up new possibilities in terms of potential therapeutics. Much of the focus has been on the postsynaptic side of the synapse, the predominant site of plasticity and learning. Recent evidence indicates that regulated protein synthesis in the presynaptic compartment is also important for synapse formation (Taylor et al., 2013) and axon arborization (Hörnberg and Holt, 2013, Hörnberg et al., 2013 and Kalous BGB324 solubility dmso et al., 2013), raising the question of whether defects in axonal protein synthesis contribute to the miswiring aspects of neurodevelopmental disorders. Dysregulated protein synthesis may also underlie a broad range of neurodegenerative disorders (Fallini et al., 2012 and Liu-Yesucevitz et al., 2011) consistent with axonal protein synthesis being required for axon maintenance (Hillefors

et al., 2007 and Yoon et al., 2012). Indeed, the first “effective” oral drug treatment that prevents neurodegeneration in a prion disease/Alzheimer’s mouse model targets a kinase (PERK) that shuts

down protein synthesis as part of the unfolded protein response (Moreno et al., 2013). Recent years have witnessed a transformation in our appreciation of RNA function in dendrites/axons on the one hand and of neuronal compartments as spatially distinct signaling/processing units on the other. Here we have highlighted the convergence of these two areas and have sought to define some of the many interesting questions and challenges that lie ahead. As technical approaches become increasingly tuclazepam sensitive for unbiased profiling there is the promise of improved “understanding” of the qualitative concepts that govern the various active RNA species and formation and function of compartments as well as quantitative details on the stoichiometries of all of the players positioned within the morphological framework of the neuron and its remarkable dendritic and axonal arbor. We thank Nicole Thomsen for editorial support. We thank Susu tom Dieck, Anais Bellon, and Bill Harris for comments and our labs for discussions. Research in C.H.’s laboratory is supported by The Wellcome Trust and the European Research Council and in E.R.’s lab by the Max Planck Society, The European Research Council, and the DFG (CRC 902, 1080, and the Cluster of Excellence for Macromolecular Complexes, Goethe University).