Nuclear Trafficking in Health and Disease

Mor, Amir; White, Michael A.; Fontoura, Beatriz M. A.

doi:10.1016/j.ceb.2014.01.007

Cited by 72 publications

(51 citation statements)

References 56 publications

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“…Inhibition of Crm1 via Leptomycin B (LepB) was previously shown to result in the retention of IAV RNPs in the nucleus, similarly to what was observed in CI-treated cells (26,27). Crm1 (also called exportin-1) is a member of the importin-␤ family and is critically involved in the transport of a variety of proteins across the nuclear envelope in both directions (26,(28)(29)(30). Notably, Crm1 interacts in a RanGTP-dependent manner with the nucleoporin Nup153, which is a caspase substrate (31).…”

mentioning

confidence: 81%

Influenza Virus-Induced Caspase-Dependent Enlargement of Nuclear Pores Promotes Nuclear Export of Viral Ribonucleoprotein Complexes

Mühlbauer

Dzieciolowski

Hardt

et al. 2015

J Virol

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Influenza A viruses (IAV) replicate their segmented RNA genome in the nucleus of infected cells and utilize caspase-dependent nucleocytoplasmic export mechanisms to transport newly formed ribonucleoprotein complexes (RNPs) to the site of infectious virion release at the plasma membrane. In this study, we obtained evidence that apoptotic caspase activation in IAV-infected cells is associated with the degradation of the nucleoporin Nup153, an integral subunit of the nuclear pore complex. Transmission electron microscopy studies revealed a distinct enlargement of nuclear pores in IAV-infected cells. Transient expression and subcellular accumulation studies of multimeric marker proteins in virus-infected cells provided additional evidence for increased nuclear pore diameters facilitating the translocation of large protein complexes across the nuclear membrane. Furthermore, caspase 3/7 inhibition data obtained in this study suggest that active, Crm1-dependent IAV RNP export mechanisms are increasingly complemented by passive, caspase-induced export mechanisms at later stages of infection. IMPORTANCEIn contrast to the process seen with most other RNA viruses, influenza virus genome replication occurs in the nucleus (rather than the cytoplasm) of infected cells. Therefore, completion of the viral replication cycle critically depends on intracellular transport mechanisms that ensure the translocation of viral ribonucleoprotein (RNP) complexes across the nuclear membrane. Here, we demonstrate that virus-induced cellular caspase activities cause a widening of nuclear pores, thereby facilitating nucleocytoplasmic translocation processes and, possibly, promoting nuclear export of newly synthesized RNPs. These passive transport mechanisms are suggested to complement Crm1-dependent RNP export mechanisms known to occur at early stages of the replication cycle and may contribute to highly efficient production of infectious virus progeny at late stages of the viral replication cycle. The report provides an intriguing example of how influenza virus exploits cellular structures and regulatory pathways, including intracellular transport mechanisms, to complete its replication cycle and maximize the production of infectious virus progeny.

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mentioning

confidence: 81%

Influenza Virus-Induced Caspase-Dependent Enlargement of Nuclear Pores Promotes Nuclear Export of Viral Ribonucleoprotein Complexes

Mühlbauer

Dzieciolowski

Hardt

et al. 2015

J Virol

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“…The association of RAN complex components, important in active transport through nuclear pores [61], in the transition zone of cilia supports this model [19, 21]. RAN appears to be involved in “controlling injections of IFT proteins into the flagellar compartment” and “is, therefore, crucial to ciliogenesis” [53].…”

Section: Implications Of the Evolutionary Origin Of Ciliamentioning

confidence: 94%

Nuclear roles for cilia-associated proteins

McClure-Begley

Klymkowsky

2017

Cilia

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Cilia appear to be derived, evolutionarily, from structures present in the ancestral (pre-ciliary) eukaryote, such as microtubule-based vesicle trafficking and chromosome segregation systems. Experimental observations suggest that the ciliary gate, the molecular complex that mediates the selective molecular movement between cytoplasmic and ciliary compartments, shares features with nuclear pores. Our hypothesis is that this shared transport machinery is at least partially responsible for the observation that a number of ciliary and ciliogenesis-associated proteins are found within nuclei where they play roles in the regulation of gene expression, DNA repair, and nuclear import and export. Recognizing the potential for such nuclear roles is critical when considering the phenotypic effects that arise from the mutational modification of ciliary proteins.Electronic supplementary materialThe online version of this article (doi:10.1186/s13630-017-0052-x) contains supplementary material, which is available to authorized users.

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“…Loading and unloading of cargo from the transport receptors is controlled by the GTPase Ran [13]. For a more extensive explanation of how nucleocytoplasmic transport functions we refer readers to other reviews focused on this topic [10,14,15]. …”

Section: Introductionmentioning

confidence: 99%

Go in! Go out! Inducible control of nuclear localization

Ventura

Kuhlman

2016

Current Opinion in Chemical Biology

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Cells have evolved a variety of mechanisms to regulate the enormous complexity of processes taking place inside them. One mechanism consists in tightly controlling the localization of macromolecules, keeping them away from their place of action until needed. Since a large fraction of the cellular response to external stimuli is mediated by gene expression, it is not surprising that transcriptional regulators are often subject to stimulus-induced nuclear import or export. Here we review recent methods in chemical biology and optogenetics for controlling the nuclear localization of proteins of interest inside living cells. These methods allow researchers to regulate protein activity with exquisite spatiotemporal control, and open up new possibilities for studying the roles of proteins in a broad array of cellular processes and biological functions.

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Nuclear Trafficking in Health and Disease

Cited by 72 publications

References 56 publications

Influenza Virus-Induced Caspase-Dependent Enlargement of Nuclear Pores Promotes Nuclear Export of Viral Ribonucleoprotein Complexes

Influenza Virus-Induced Caspase-Dependent Enlargement of Nuclear Pores Promotes Nuclear Export of Viral Ribonucleoprotein Complexes

Nuclear roles for cilia-associated proteins

Go in! Go out! Inducible control of nuclear localization

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