Transport routes through the nuclear pore complex

Pemberton, Lucy F.; Blobel, Günter; Rosenblum, Jonathan S.

doi:10.1016/s0955-0674(98)80016-1

Cited by 230 publications

(221 citation statements)

References 69 publications

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“…These data suggest that molecules responsible for nuclear The mechanisms that regulate STAT4 cytoplasmic-nuclear import and nuclear-cytoplasmic export are critical for IFN-␥ production and proliferation of T cells. As was shown for STAT1 nuclear translocation, facilitated transport of STAT1 into the nucleus requires the presence of signal motifs (nuclear localization signals (32)) that are recognized by specific soluble shuttling receptors of the importin/karyopherin family (33)(34)(35)(36)(37). Cytokine-induced transcription is a transient process, lasting only minutes to hours (38).…”

Section: Discussionmentioning

confidence: 98%

Impairment of IL-12-Dependent STAT4 Nuclear Translocation in a Patient with Recurrent Mycobacterium avium Infection

Toyoda

Ido

Hayashi

et al. 2004

The Journal of Immunology

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We examined the immunological abnormality in a patient with recurrent Mycobacterium avium infection. T cells from the patient showed decreased ability both to produce IFN-γ and to proliferate in response to IL-12. Despite decreased expression of IL-12R β1 and β2 chains in the patient’s PHA-activated T cells, there was no difference in IL-12-induced tyrosine and serine phosphorylation of STAT4 in PHA-activated T cells between the patient and healthy subjects, suggesting that IL-12R signals are transmitted to STAT4 in the patient’s PHA-activated T cells. Using EMSA, confocal laser microscopy, and Western blotting, we demonstrated that the nuclear translocation of STAT4 in response to IL-12 is reduced in PHA-activated T cells from the patient when compared with those from healthy subjects. Leptomycin B was used to examine whether nuclear export of STAT4 is increased in the patient’s T cells. However, leptomycin B treatment did not reverse impaired IL-12-induced nuclear accumulation of STAT4. Although the exact mechanism responsible for the impaired STAT4 nuclear translocation in this patient remains unclear, the absence of mutation in the IL-12Rβ1, IL-12Rβ2, STAT4, and STAT4-binding sequence of the IFN-γ gene and preservation of STAT4 tyrosine and serine phosphorylation suggest the existence of a defective STAT4 nuclear translocation. This defect is likely responsible for the impaired STAT4 nuclear translocation in IL-12-stimulated T cells, leading to impairment of both IFN-γ production and cell proliferation. To the best of our knowledge, this is the first report of a patient with atypical mycobacterial infection associated with impairment of STAT4 nuclear translocation.

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Section: Discussionmentioning

confidence: 98%

Impairment of IL-12-Dependent STAT4 Nuclear Translocation in a Patient with Recurrent Mycobacterium avium Infection

Toyoda

Ido

Hayashi

et al. 2004

The Journal of Immunology

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“…Importin ␤ is also found in S. cerevisiae (importin ␤/RSL1). The import factors that show the highest sequence similarity to importin 7 (RanBP7) are NMD5 (KAP119) and SXM1 (KAP108) (35). But sequence comparison of the importin ␤-binding site of importin 7 (aa 1008 -1038) reveals that none of the yeast import receptors show any similarity with this sequence.…”

Section: Fig 5 Mapping Of the Imp␤ Binding Domain In Imp7mentioning

confidence: 99%

The Requirement of H1 Histones for a Heterodimeric Nuclear Import Receptor

Bäuerle¹,

Doenecke²,

Albig³

2002

Journal of Biological Chemistry

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After synthesis in the cytoplasm, H1 histones are imported into the nucleus through an energy-dependent process that can be mediated by an importin ␤-importin 7 (Imp␤-Imp7) heterodimer. H1 histones contain two structurally different types of nuclear localization signals (NLS). The first type of NLS resides within the unstructured C-terminal domain and is rich in basic amino acids. In contrast, the highly conserved central domain of the H1 histone contains comparatively few basic amino acids but also represents a functional NLS. The competence for the nuclear import of this globular domain seems to be based on its secondary structure. Here, we show that the Imp␤-Imp7 heterodimer is the only receptor for H1 import. Furthermore, we identified the import receptors mediating the in vitro transport of different NLS of the H1 histone. Using the digitoninpermeabilized cell import assay we show that Imp␤ is the most efficient import receptor for the globular domain of H1 histones, whereas the heterodimer of Imp␤ and Imp7 is the functional receptor for the entire Cterminal domain. However, short fragments of the Cterminal domain are imported in vitro by at least four different importins, which resembles the import pathway of ribosomal proteins and core histones. In addition, we show that heterodimerization of Imp␤ with Imp7 is absolutely necessary for their proper function as an import receptor for H1 histones. These findings point to a chaperone-like function of the heterodimeric complex in addition to its function as an import receptor. It appears that the Imp␤-Imp7 heterodimer is specialized for NLS consisting of extended basic domains.Histones are the protein component of the fundamental structural unit of eukaryotic chromatin, the nucleosome. The nucleosome is composed of a core particle consisting of a histone octamer with 146 bp of DNA bent around its surface and an approximately 50-bp linker DNA connecting two adjacent core particles. This linker DNA is associated with H1 histones; hence they are termed linker histones (1). The four core histones H2A, H2B, H3, and H4 form the histone octamer. Histones are small, very basic proteins. The linker histone H1 is highly enriched in lysine, H2A and H2B are moderately lysinerich, and H3 and H4 are rich in arginine. The size of core histones varies between 11 kDa (H4) and 15 kDa (H3), whereas the H1 histones have a size of ϳ22 kDa. In mammals the class of H1 histones, the linker histones, comprises seven different subtypes, termed H1.1-H1.5, H1°, and H1t (2). Histones are composed of three domains, the very basic, unstructured C-and N-terminal domains and the hydrophobic, central globular domain, which forms the histone fold motif in the case of the core histones (3) and is involved in histone-histone interactions. During the S phase of the cell cycle, a vast amount of newly synthesized histones has to be imported into the nucleus for the formation of nucleosomes on newly replicated DNA. Thus, histones are among the most abundant substrates for nuclear transport during the...

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“…It is typically receptormediated transport and coupled to an input of metabolic energy, thus being capable of cargo transport even against steep gradients of chemical activity [15,16]. Translocation of cargos is often facilitated by soluble receptors that can bind NPCs and also recognize targeting signals within the cargo [17,18]. The receptors have variously been termed karyopherins, importins, exportins and transportins.…”

Section: Introductionmentioning

confidence: 99%