Nucleocytoplasmic protein shuttling: the direct route in synapse-to-nucleus signaling

In neurons multiple signaling pathways converge in the nucleus to regulate the expression of genes associated with long-term structural changes of synapto-dendritic input. Of pivotal importance for this type of transcriptional regulation is synapse-to-nucleus communication. Several studies suggest that the nuclear transport of proteins from synapses is involved in this signaling process, including evidence that synapses contain proteins with nuclear localization sequences and components of the nuclear import machinery. Here, we review the evidence for synapse-to-nucleus signaling by means of retrograde transport of proteins from distal processes. We discuss the mechanisms involved in their translocation and their role in the control of nuclear gene expression. Finally, we summarize the current thinking regarding the functional implications of nuclear signaling and address open questions in this evolving area of neuroscience.