Regulated transport of signaling proteins from synapse to nucleus

Synapse-to-nucleus communication is essential for neural development, plasticity, and repair. In addition to fast electrochemical signaling, neurons employ a slower mechanism of protein transport from synapse-to-nucleus. This mechanism provides potential advantages, including the encoding of spatial information. Many synaptonuclear signaling proteins are transported from the postsynaptic compartment to the nucleus in an activity-dependent manner. The phosphorylation state of two such proteins, CRTC1 and Jacob, is dependent on the stimulus type. While most studies have focused on postsynaptic synaptonuclear communication, a transcriptional co-repressor, CtBP1, was recently discovered to undergo activity-dependent translocation from the presynaptic compartment to the nucleus. Recent evidence indicates that synapse-to-nucleus communication could be cell type-specific, including the identification of a distinct mechanism of excitation-transcription coupling in inhibitory neurons.