The role of NDE1 in synapse-to-nucleus signalling

Abstract

Synaptic signals travel from the synapses toward the nucleus in a manner known as synapse-to-nucleus signalling, which is required for the encoding of long-term memories and of which multiple pathways exist. Importin-mediated signalling and its relationship to the development of long-term potentiation (LTP), learning, and memory, have been less well-studied and thus requires greater attention. Mass spectronomey analysis found enrichment in NudE Neurodevelopment Protein 1 (NDE1) in activated synaptosomes. NDE1 is a potential candidate for further study due to the presence of a nuclear localization signal, and previous reports of nuclear and cytoplasmic localization and implications in the gene disrupted in schizophrenia-1 and lissencephaly-1 (DISC-LIS1) complex in the Reelin-DISC pathway, which has been shown to be related to schizophrenia. Having yet to be fully studied in the hippocampus, we aim to characterize NDE1 and its role and behavior in the neuron, and the potential cargo-carrier relationship between NDE1 and importin-β1, which may prove useful to potentially identify therapeutic means for schizophrenia treatment in the future. Cargo-based experiments found that NDE1 localizes in the cytoplasm of mammalian and does not respond by nuclear translocation to activation of either cell type, while KCl-induced stimulation leads to translocation in neurons.