A systems analysis of importin-α–β mediated nuclear protein import

Riddick, Gregory; Macara, Ian G.

doi:10.1083/jcb.200409024

Cited by 111 publications

(155 citation statements)

References 47 publications

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“…The present model originates from the ODE model of Ran-driven nucleocytoplasmic import successively developed by Gorlich et al [48,23], Smith et al [56], Riddick and Macara [49,50], and Kopito and Elbaum [33].…”

Section: Reaction-diffusion Modelmentioning

confidence: 99%

“…The receptor involved in nuclear import is made of two subunits: the adaptor Importin-α which binds the cargo Nuclear Localization Signal (NLS) and the receptor Importin-β which permits the translocation through the NPC. Here, we simplify matters by considering the binding of the cargo with the whole importin complex (see [49,50] for a detailed analysis of the various import pathways).…”

Section: Reaction-diffusion Modelmentioning

confidence: 99%

“…Nuclear RanGDP, imported by the transport receptor NTF2, interacts with the nuclear RanGEF (RCC1) which catalyzes the exchange between nucleotide GDP and GTP forming the nuclear RanGTP. The complete biochemical scheme of this exchange is composed of a sequential set of enzymatic steps [32,23,49] which, following [56], we schematize as a single reaction.…”

Section: Reaction-diffusion Modelmentioning

confidence: 99%

“…Estimates of translocation rates of most molecular species are available from the literature and have already been used in a number of studies [39,56,23,49,50]. The values used in the model are taken from [56] and are shown in Table 3.…”

Section: Facilitated Translocation Through the Nuclear Envelopementioning

confidence: 99%

“…Many mathematical models have been proposed, which qualitatively reproduce the dynamics of intracellular trafficking and signal transduction, often formulated in terms of ordinary differential equations describing the time course of the molecular concentrations (compartmental models) [39,56,23,7,49,30,50]. These are based on schematic descriptions of signal transduction pathways which do not take into account the spatial localization of the reactions [25].…”

Section: Introductionmentioning

confidence: 99%

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A spatial model of cellular molecular trafficking including active transport along microtubules

Cangiani

Natalini

2010

Journal of Theoretical Biology

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To cite this version:A. Cangiani, R. Natalini. A spatial model of cellular molecular trafficking including active transport along microtubules. Journal of Theoretical Biology, Elsevier, 2010, 267 (4) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. A SPATIAL MODEL OF CELLULAR MOLECULAR TRAFFICKING INCLUDING ACTIVE TRANSPORT ALONG MICROTUBULESA. CANGIANI * , R. NATALINI † Abstract. We consider models of Ran-driven nuclear transport of molecules such as proteins in living cells. The mathematical model presented is the first to take into account for the active transport of molecules along the cytoplasmic microtubules. All parameters entering the models are thoroughly discussed. The model is tested by numerical simulations based on Discontinuous Galerkin finite element methods. The numerical experiments are compared to the behavior observed experimentally.

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Section: Reaction-diffusion Modelmentioning

confidence: 99%

Section: Reaction-diffusion Modelmentioning

confidence: 99%

Section: Reaction-diffusion Modelmentioning

confidence: 99%

Section: Facilitated Translocation Through the Nuclear Envelopementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A spatial model of cellular molecular trafficking including active transport along microtubules

Cangiani

Natalini

2010

Journal of Theoretical Biology

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Nuclear localisation sequences of chloride intracellular channels 1 and 4 facilitate nuclear import via interactions with import mediator importin‐α: An empirical and theoretical perspective

Faerch

Worth

Achilonu

et al. 2022

J of Molecular Recognition

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Chloride intracellular channel proteins (CLICs) display ubiquitous expression, with each member exhibiting specific subcellular localisation. While all CLICs, except CLIC3, exhibit a highly conserved putative nuclear localisation sequence (NLS), only CLIC1, CLIC3 and CLIC4 exist within the nucleus. The CLIC4 NLS, 199‐KVVAKKYR‐206, appears crucial for nuclear entry and interacts with mouse nuclear import mediator Impα isoform 1, omitting the IBB domain (mImpα1ΔIBB). The essential nature of the basic residues in the CLIC4 NLS has been established by the fact that mutating out these residues inhibits nuclear import, which in turn is linked to cutaneous squamous cell cancer. Given the conservation of the CLIC NLS, CLIC1 likely follows a similar import pathway to CLIC4. Peptides of the CLIC1 (Pep1; Pep1_S C/S mutant) and CLIC4 (Pep4) NLSs were designed to examine binding to human Impα isoform 1, omitting the IBB domain (hImpα1ΔIBB). Molecular docking indicated that the core CLIC NLS region (KKYR) forms a similar binding pattern to both mImpα1ΔIBB and hImpα1ΔIBB. Fluorescence quenching demonstrated that Pep1_S (Kd ≈ 237 μM) and Pep4 (Kd ≈ 317 μM) bind hImpα1ΔIBB weakly. Isothermal titration calorimetry confirmed the weak binding interaction between Pep4 and hImpα1ΔIBB (Kd ≈ 130 μM) and the presence of a proton‐linked effect. This weak interaction may be due to regions distal from the CLIC NLS needed to stabilise and strengthen hImpα1ΔIBB binding. Additionally, this NLS may preferentially bind another hImpα isoform with different flexibility properties.

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Karyopherin Alpha 1 Regulates Satellite Cell Proliferation and Survival by Modulating Nuclear Import

Choo¹,

Cutler

Rother

et al. 2016

Stem Cells

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Satellite cells are stem cells with an essential role in skeletal muscle repair. Precise regulation of gene expression is critical for proper satellite cell quiescence, proliferation, differentiation and self -renewal. Nuclear proteins required for gene expression are dependent on the nucleocytoplasmic transport machinery to access to nucleus, however little is known about regulation of nuclear transport in satellite cells. The best characterized nuclear import pathway is classical nuclear import which depends on a classical nuclear localization signal (cNLS) in a cargo protein and the heterodimeric import receptors, karyopherin alpha (KPNA) and beta (KPNB). Multiple KPNA1 paralogs exist and can differ in importing specific cNLS proteins required for cell differentiation and function. We show that transcripts for six Kpna paralogs underwent distinct changes in mouse satellite cells during muscle regeneration accompanied by changes in cNLS proteins in nuclei. Depletion of KPNA1, the most dramatically altered KPNA, caused satellite cells in uninjured muscle to prematurely activate, proliferate and undergo apoptosis leading to satellite cell exhaustion with age. Increased proliferation of satellite cells led to enhanced muscle regeneration at early stages of regeneration. In addition, we observed impaired nuclear localization of two key KPNA1 cargo proteins: p27, a cyclin-dependent kinase inhibitor associated with cell cycle control and lymphoid enhancer factor 1, a critical co-transcription factor for β-catenin. These results indicate that regulated nuclear import of proteins by KPNA1 is critical for satellite cell proliferation and survival and establish classical nuclear import as a novel regulatory mechanism for controlling satellite cell fate.

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A systems analysis of importin-α–β mediated nuclear protein import

Cited by 111 publications

References 47 publications

A spatial model of cellular molecular trafficking including active transport along microtubules

A spatial model of cellular molecular trafficking including active transport along microtubules

Nuclear localisation sequences of chloride intracellular channels 1 and 4 facilitate nuclear import via interactions with import mediator importin‐α: An empirical and theoretical perspective

Karyopherin Alpha 1 Regulates Satellite Cell Proliferation and Survival by Modulating Nuclear Import

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