LOCAL REGULATION AND FUNCTION OF IMPORTIN-β1 IN HIPPOCAMPAL NEURONS DURING TRANSCRIPTION-DEPENDENT PLASTICITY

Abstract

SUMMARYActivity-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.

Jacob, a Synapto-Nuclear Protein Messenger Linking N-methyl-D-aspartate Receptor Activation to Nuclear Gene Expression

“…The prevalent model of activity-induced protein transport from synapses to the nucleus implies the binding of a nuclear localization signal (NLS) in synapto-nuclear protein messengers with one of the importin-α family members in response to synaptic activation. This is followed by binding to importin-β and association with a dynein motor that eventually mediates the transport of the protein complex along microtubule toward the nucleus (Cingolani et al, 1999;Fainzilber et al, 2011;Ch'ng and Martin, 2011;Kaushik et al, 2014;Lever et al, 2015;Panayotis et al, 2015;Lee et al, 2020).…”

Local regulation and function of importin-β1 in hippocampal neurons during transcription-dependent plasticity

“…All materials, except Chapter 1.3, Adducin-1 data in Fig. 3-11, and Chapter 5, are deposited in Lee et al (2020).…”