Reduction of exportin 6 activity leads to actin accumulation via failure of RanGTP restoration and NTF2 sequestration in the nuclei of senescent cells

Park, Sang Hyoung; Park, Tae Jun; Lim, In Kyoung

doi:10.1016/j.yexcr.2010.12.023

Cited by 8 publications

(8 citation statements)

References 54 publications

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“…Instead, we found that exportin 6 mediated the export of actin both in the murine fibroblastic cell line NIH 3T3 and the Drosophila cell line S2R+, demonstrating that this export mechanism is largely shared among eukaryotes 9 . This data therefore confirms and extends the previous results implicating exportin 6 as the major nuclear export receptor for actin 11 - 13 …”

Section: Molecular Basis and Dynamics Of The Nuclear Localization Of supporting

confidence: 89%

Nuclear actin levels as an important transcriptional switch

2012

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Section: Molecular Basis and Dynamics Of The Nuclear Localization Of supporting

confidence: 89%

Nuclear actin levels as an important transcriptional switch

2012

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“…However, depletion of Exp6 in mouse fibroblasts resulted in clear accumulation of GFP-actin in the nucleus (Fig. 1D), supporting an earlier observation in human diploid fibroblasts (33). In Drosophila S2R+ cells, depletion of Exp6 also accumulated actin in the nucleus, and the phenotype manifested as a phalloidin-stainable bar in about 50% of the cells ( Fig.…”

Section: Nuclear Export Of Actin Is Mediated By Exp6 and Is Not Sensisupporting

confidence: 87%

Active maintenance of nuclear actin by importin 9 supports transcription

Dopie

Skarp

Rajakylä

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

226

320

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Besides its essential and well established role as a component of the cytoskeleton, actin is also present in the cell nucleus, where it has been linked to many processes that control gene expression. For example, nuclear actin regulates the activity of specific transcription factors, associates with all three RNA polymerases, and is a component of many chromatin remodelling complexes. Despite the fact that two export receptors, Crm1 and exportin 6, have been linked to nuclear export of actin, the mechanism by which actin enters the nucleus to elicit these essential functions has not been determined. It is also unclear whether actin is actively exchanged between the nucleus and the cytoplasm, and whether this connection has any functional significance for the cell. By applying a variety of live-cell imaging techniques we revealed that actin constantly shuttles in and out of the nucleus. The fast transport rates, which depend on the availability of actin monomers, suggest an active transport mechanism in both directions. Importantly, we identified importin 9 as the nuclear import factor for actin. Furthermore, our RNAi experiments showed that the active maintenance of nuclear actin levels by importin 9 is required for maximal transcriptional activity. Measurements of nuclear export rates and depletion studies also clarified that nuclear export of actin is mediated by exportin 6, and not by Crm1. These results demonstrate that cytoplasmic and nuclear actin pools are dynamically connected and identify the nuclear import and export mechanisms of actin.

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“…In the intestinal epithelial cells of embargoed mutant larvae, actin accumulates in the nuclei , as reported in the leptomycin B‐treated murine cells . These results support that both Drosophila Embargoed and mammalian CRM1 mediate the nuclear export of actin, though exportin‐6 also exports actin in mammals .…”

Section: Imp‐βs In Drosophilasupporting

confidence: 81%

Biological Significance of the Importin‐β Family‐Dependent Nucleocytoplasmic Transport Pathways

Kimura

Imamoto

2014

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110

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Importin-β family proteins (Imp-βs) are nucleocytoplasmic transport receptors (NTRs) that import and export proteins and RNAs through the nuclear pores. The family consists of 14-20 members depending on the biological species, and each member transports a specific group of cargoes. Thus, the Imp-βs mediate multiple, parallel transport pathways that can be regulated separately. In fact, the spatiotemporally differential expressions and the functional regulations of Imp-βs have been reported. Additionally, the biological significance of each pathway has been characterized by linking the function of a member of Imp-βs to a cellular consequence. Connecting these concepts, the regulation of the transport pathways conceivably induces alterations in the cellular physiological states. However, few studies have linked the regulation of an importin-β family NTR to an induced cellular response and the corresponding cargoes, despite the significance of this linkage in comprehending the biological relevance of the transport pathways. This review of recent reports on the regulation and biological functions of the Imp-βs highlights the significance of the transport pathways in physiological contexts and points out the possibility that the identification of yet unknown specific cargoes will reinforce the importance of transport regulation.

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Reduction of exportin 6 activity leads to actin accumulation via failure of RanGTP restoration and NTF2 sequestration in the nuclei of senescent cells

Cited by 8 publications

References 54 publications

Nuclear actin levels as an important transcriptional switch

Nuclear actin levels as an important transcriptional switch

Active maintenance of nuclear actin by importin 9 supports transcription

Biological Significance of the Importin‐β Family‐Dependent Nucleocytoplasmic Transport Pathways

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