SUMMARY Activity-dependent transcription is critical for the encoding of long-term memories. Regulated nuclear entry of soluble proteins is one method to relay synaptic signals to the nucleus to couple neuronal excitation with transcription. To date, the role of importin-β1 in nuclear shuttling of proteins during activity-dependent transcription has always been inferred but not directly investigated. In this study, we demonstrate activity-dependent nuclear accumulation of importin-β1 from the soma and the synapto-dendritic compartments. Importantly, inhibition of importin-β1 mediated nuclear import during synaptic stimulation impairs long-term plasticity. We show evidence that importin-β1 mRNA-ribosome complex is distributed throughout the synapto-dendritic compartment and synaptic stimulation induces importin-β1 local protein synthesis. Finally, we identified candidate proteins that associate with importin-β1 at the synapse and characterize NDRG1 as an importin-β1 interactor that undergoes activitydependent translocation into the nucleus. Collectively, our results highlight the crucial role of importin-β1 in nuclear import of proteins during long-term plasticity.

Local Regulation and Function of Importin-β1 During Transcription-Dependent Plasticity