Importin-mediated nuclear transport in neurons

University of California, Los Angeles, Gonda Research Building 3506C, 695 Charles Young Drive South, Los Angeles, CA 90095-1761, USA.
Current Opinion in Neurobiology (Impact Factor: 6.63). 07/2006; 16(3):329-35. DOI: 10.1016/j.conb.2006.05.001
Source: PubMed


The polarized morphology of neurons poses a particular challenge to intracellular signal transduction. Local signals generated at distal sites must be retrogradely transported to the nucleus to produce persistent changes in neuronal function. Such communication of signals between distal neuronal compartments and the nucleus occurs during axon guidance, synapse formation, synaptic plasticity and following neuronal injury. Recent studies have begun to delineate a role for the active nuclear import pathway in transporting signals from axons and dendrites to the nucleus. In this pathway, soluble cargo proteins are recognized by nuclear transport carriers, called importins, which mediate their translocation from the cytoplasm into the nucleus. In neurons, importins might serve an additional function by carrying signals from distal sites to the soma.

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    • "Molecules containing a classical NLS bind to these armadillo-repeats whereas the N-terminus of importin-a can associate simultaneously with importin-b. The interaction between both importins subsequently increases the affinity of importin-a binding to NLScontaining proteins from the micromolar to the nanomolar range (Otis et al., 2006). "
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    • "Analysis of the Fto crystal structure has established that N-terminal domain (NTD) contains a nuclear localisation signal (NLS) [14]. It has previously been reported that masking of NLS can inhibit the nuclear import of proteins normally transported from cytoplasm to nucleus [15]. The abolishment of nuclear import can result from the cargo protein post-translational modifications, such as phosphorylation/dephosphorylation [16]. "
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    PLoS ONE 05/2013; 8(5):e63694. DOI:10.1371/journal.pone.0063694 · 3.23 Impact Factor
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    • "Previous research has shown that proteins enriched at or near neuronal synapses accumulate in the nucleus in response to stimulation. These proteins include factors controlling gene expression, scaffold molecules, and the proteolyzed intracellular domains of synaptic receptors (4,5). Transcription factors, such as cyclic AMP responsive element-binding protein (CREB)2, and translation regulators, such as cytoplasmic polyadenylation element-binding protein (CPEB)3 and CPEB4, move to the nucleus after activation of the N-methyl-d-aspartate receptor (NMDAR) (6–9), suggesting that the nucleocytoplasmic partition of these proteins by specific neuronal signaling determines their role in gene expression. "
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