Article

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: 6.77). 07/2006; 16(3):329-35. DOI: 10.1016/j.conb.2006.05.001
Source: PubMed

ABSTRACT 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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    • "Conventionally, importin-a binds the cargo protein and subsequently forms a heterotrimeric nuclear pore-targeting complex with importin-b1 (Goldfarb et al. 2004). Previous reports have shown that the murine importin-a/karyopherin-a gene family of nuclear transport adaptor proteins comprises at least five members (Otis et al. 2006). Based on sequence homology, importin-a family members are classified into three subfamilies: a-P (Imp-a2/karyopherin-a2/Gene ID:16647), a-Q (Imp-a3/Q2/karyopherin-a3/Gene ID:16648 and Imp-a4/Q1/karyopherin-a4/ Gene ID:16649), and a-S (Imp-a1/S1/karyopherin-a1/Gene ID:16646 and Imp-a 6/S2/karyopherin-a6/Gene ID:16650). "
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    • "Nuclear transport of steroid receptors and transcription factors occurs throughout the brain and although the importin pathway has been linked to the nuclear transport of various receptors in-vitro (Tanaka et al., 2005; Otis et al., 2006; Pickard et al., 2006), there is very little information about the expression of importins in brain. A recent study was the first to demonstrate that imp β-1 mRNA was expressed in brain and furthermore that imp β-1 and other members of the importin family were expressed in the PVN (Hosokawa et al., 2008). "
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