Toh Hean CHNG

The role of Importin-β1 in synapse to nucleus transport of proteins during transcription-dependent plasticity

Enduring changes in synaptic efficacy is associated with the encoding of long-term memories and this requires activity-dependent transcription of new genes and translation of new proteins. It has been demonstrated that various transcriptional modulators are localized at the synapse and are transported to the nucleus during neuronal activity and this activity-dependent translocation is critical for different aspects of long-term plasticity. The failure of this signal transmission is the underlying cause of numerous neuropsychiatric and neurocognitive disorders. Our lab has studied the transport of proteins and plasticity factors from the synapse to the nucleus by looking at the adaptor protein Importin-β1, a component of the classical nuclear import machinery. Here, we present evidence that Impβ1 is localized at different subcellular compartments and play an important role in different forms of long-term plasticity in hippocampal neurons. We also show evidence that importin β1 mRNA is localized in dendrites and synapses and undergoes robust local translation in stimulated synapses, suggesting that the transport machinery plays an active role in shuttling plasticity-associated proteins into the nucleus. Finally, we describe a novel method of isolating plasticity factors that bind to Impβ1 at the synapse and identify putative candidates that may undergo synapse to nucleus signaling.