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.

Download full-text


Available from: Kelsey C Martin, Aug 26, 2015
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Long-lasting changes in neuronal excitability require activity-dependent gene expression and therefore the transduction of synaptic signals to the nucleus. Synaptic activity is rapidly relayed to the nucleus by membrane depolarization and the propagation of Ca(2+) -waves. However, it is unlikely that Ca(2+)-transients alone can explain the specific genomic response to the pleithora of extracellular stimuli that control gene expression. In recent years a steadily growing number of studies report the transport of proteins from synapse to nucleus. Potential mechanisms for active retrograde transport and nuclear targets for these proteins have been identified and recent reports assigned first functions to this type of long-distance signaling. In this review we will discuss how the dissociation of synapto-nuclear protein messenger from synaptic and extrasynaptic sites, their transport, nuclear import and the subsequent genomic response relate to the prevailing concept behind this signaling mechanism, the encoding of signals at their site of origin and their decoding in the nucleus.
    Neuroscience 09/2014; 280. DOI:10.1016/j.neuroscience.2014.09.011 · 3.33 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The communication between synapses and the cell nucleus has attracted considerable interest for many years. This interest is largely fueled by the idea that synapse-to-nucleus signaling might specifically induce the expression of genes that make long-term memory "stick." However, despite many years of research, it is still essentially unclear how synaptic signals are conveyed to the nucleus, and it remains to a large degree enigmatic how activity-induced gene expression feeds back to synaptic function. In this chapter, we will focus on the activity-dependent synapto-nuclear trafficking of protein messengers and discuss the underlying mechanisms of their retrograde transport and their supposed functional role in neuronal plasticity.
    Advances in Experimental Medicine and Biology 01/2012; 970:355-76. DOI:10.1007/978-3-7091-0932-8_16 · 2.01 Impact Factor
  • Source
    • "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). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The tachykinin NK3 receptor (NK3R) is a G-protein coupled receptor that is activated, internalized, and trafficked to the nuclei of magnocellular neurons in the paraventricular nucleus of the hypothalamus (PVN) in response to acute hyperosmolarity. The lack of information on the nuclear import pathway raises concerns about the physiological role of nuclear NK3R. NK3R contains a nuclear localizing sequence (NLS) and this raises the possibility that importins are involved in transport of NK3R through the nuclear pore complex. The following experiments utilized: (1) co-immunoprecipitation to determine if NK3R is associated with importin ß-1 following activation in response to acute hyperosmolarity in vivo, and (2) immuno-neutralization of importin ß-1 in vitro to determine if nuclear transport of NK3R was blocked. Rats were given an i.v. injection of hypertonic saline (2 M) and 10 min after the infusion, the PVN was removed and homogenized. Importin ß-1 co-immunoprecipitated with the NK3R following treatment with 2 M NaCl, but not following isotonic saline treatment. Immuno-neutralization of importin ß-1 decreased the transport of NK3R into the nuclei in a time dependent fashion. The results indicate that in response to acute hyperosmotic challenge, NK3R associates with importin ß-1 which enables the nuclear transport of NK3R. This is the first in vivo study linking importin ß-1 and the nuclear transport of a G protein coupled receptor, the NK3R, in brain.
    Neuroscience 11/2010; 170(4):1020-7. DOI:10.1016/j.neuroscience.2010.08.015 · 3.33 Impact Factor
Show more