Bidirectional Increase in Permeability of Nuclear Envelope upon Poliovirus Infection and Accompanying Alterations of Nuclear Pores

Belov, George A.; Lidsky, Peter V.; Mikitas, Olga V.; Egger, Denise; Lukyanov, Konstantin A.; Bienz, Kurt; Agol, Vadim I.

doi:10.1128/jvi.78.18.10166-10177.2004

Cited by 106 publications

(154 citation statements)

References 84 publications

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“…Both glucocorticoids (41) and mineralocorticiods (42) rapidly and transiently increase the permeability of the nuclear pore to dextrans in the 10 -20-kDa size range. This action precedes the initiation of gene transcription that is induced by these steroid hormones and thus may play a role in mediating that effect (40,41). Here we found that vasopressin, angiotensin, phenylephrine, and ATP each increase nuclear permeability.…”

Section: Discussionsupporting

confidence: 49%

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Hormonal Regulation of Nuclear Permeability

O'Brien

Gomes

Sehgal

et al. 2007

Journal of Biological Chemistry

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Transport into the nucleus is critical for regulation of gene transcription and other intranuclear events. Passage of molecules into the nucleus depends in part upon their size and the presence of appropriate targeting sequences. However, little is known about the effects of hormones or their second messengers on transport across the nuclear envelope. We used localized, two-photon activation of a photoactivatable green fluorescent protein to investigate whether hormones, via their second messengers, could alter nuclear permeability. Vasopressin and other hormones that increase cytosolic Ca 2؉ and activate protein kinase C increased permeability across the nuclear membrane of SKHep1 liver cells in a rapid unidirectional manner. An increase in cytosolic Ca 2؉ was both necessary and sufficient for this process. Furthermore, localized photorelease of caged Ca 2؉ near the nuclear envelope resulted in a local increase in nuclear permeability. Neither activation nor inhibition of protein kinase C affected nuclear permeability. These findings provide evidence that hormones linking to certain G protein-coupled receptors increase nuclear permeability via cytosolic Ca 2؉ . Short term regulation of nuclear permeability may provide a novel mechanism by which such hormones permit transcription factors and other regulatory molecules to enter the nucleus, thereby regulating gene transcription in target cells.The nuclear envelope represents a structural and functional barrier to passage between the nucleus and the cytosol. Regulation of the permeability of this barrier is one potential mechanism to control access to the nucleus for proteins that affect nuclear function, including transcription factors and various kinases and phosphatases. Nucleocytosolic passage generally occurs through the nuclear pore complex (1, 2), a 125-MDa membrane-spanning protein complex consisting of eight ion channels and a large central passage (3). Movement of molecules through the nuclear pore is restricted on the basis of size and the presence or absence of appropriate localization sequences. Studies using electron scanning microscopy (4), fluorescence recovery after photo-bleaching techniques (5), and microinjection of fluorescently labeled dextrans (6) have shown that molecules up to 40 -60 kDa in size can cross the nuclear envelope without a signaling sequence. Proteins less than 4 -10 kDa in size freely pass from cytosol to nucleus (6 -8), while intermediate sized proteins (19 -40 kDa) do not need a targeting sequence to cross the nuclear pore, but the permeability of the pore to such molecules may be modulated (6 -8). One factor that appears to regulate the permeability of the nuclear pore to proteins in this intermediate size range is the amount of Ca 2ϩ within the nuclear envelope (6 -9), although there is now conflicting evidence about this (5). Little is known about the role of cytosolic factors such as second messengers in the regulation of nuclear pore permeability.The spatial pattern of second messenger signals is important for how thes...

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Section: Discussionsupporting

confidence: 49%

“…of GFP into the nucleus is increased in infected cells, and cells also lose the ability to retain NLS-tagged GFP within the nucleus (40). Both glucocorticoids (41) and mineralocorticiods (42) rapidly and transiently increase the permeability of the nuclear pore to dextrans in the 10 -20-kDa size range.…”

Section: Discussionmentioning

confidence: 99%

Hormonal Regulation of Nuclear Permeability

O'Brien

Gomes

Sehgal

et al. 2007

Journal of Biological Chemistry

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“…Alteration of several nuclear-cytoplasmic pathways has been documented during viral infection and an increase in nuclear permeability is a general strategy adopted by several viruses such as poliovirus, 19,45 rhinovirus 46 and cardiovirus 47 to gain access to the cell genetic information. In this case, the increased redistribution of NLS and NES-containing EGFP has been attributed to a perturbation of the docking of receptor-cargo complexes to the NPC.…”

Section: Discussionmentioning

confidence: 99%

Alteration of the nuclear pore complex in Ca2+-mediated cell death

et al. 2009

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Cell death requires coordinated intracellular signalling before disassembly of cell architecture by degradative enzymes. Although the death signalling cascades that involve the mitochondria, the ER and the plasma membrane have been extensively characterized, only a handful of studies have examined the functional and structural alterations of the nuclear pore complex (NPC) during neuronal death. Here, we show that during excitotoxic neuronal degeneration calpains redistributed across the nuclear envelope and mediated the degradation of NPC components causing altered permeability of the nuclear membrane. In primary dissociated neurons, simultaneous recording of cytosolic [Ca 2 þ ] and localization of fluorescent proteins showed that the onset of Ca 2 þ overload signalled a progressive increase in the diffusion of small reporter molecules across the nuclear envelope. Later, calpain-mediated changes in nuclear pore permeability allowed accumulation of large proteins in the nucleus. Further, in a model of excitotoxic neuronal degeneration in Caenorhabditis elegans, we found similar nuclear changes and redistribution of fluorescent probes across the nuclear membrane in dying neurons. Our findings strongly suggest that increased leakiness of the nuclear barrier affects nucleocytoplasmic transport, alters the localization of proteins across the nuclear envelope and it is likely to be involved in Ca 2 þ -dependent cell death, including ischemic neuronal demise. The execution of cell death requires coordinated signalling between intracellular compartments and the plasma membrane. 1 Death-initiating signals can be generated at the plasma membrane, 2 or as a result of intracellular stress. [3][4][5] As part of this signalling process, the redistribution of molecules across cellular compartments occurs in different cell death paradigms. Examples include poly-ADP-ribose polymers 6 and p53, 7 which translocate from the nucleus to the mitochondria, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), 8 which redistributes from the cytosol to the nucleus, and the pro-apoptotic protein apoptosis-inducing factor (AIF), 9,10 which diffuses from the mitochondria to the nucleus. As part of the death program, molecular redistribution is also required to process intracellular structures. Thus, the targets for the proteolytic systems involved in cell death include membranes that form selective permeability barriers to molecular trafficking.Selective loss of nuclear permeability has been associated with virus-mediated and caspase-dependent cell death. In apoptosis, processing of several components of the envelope is downstream of caspase activation and thereby downstream of the mitochondrial signals for caspase activation. Disassembly of the nuclear envelope, 11 intranuclear proteins [12][13][14][15] and chromosomal DNA 16,17 are likely to have an important function in promoting disposal of the nucleus and its content. Probably because nuclear permeabilization is thought to be a late event in death programs, only a handful of studies have e...

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“…These NPC extensions might function as initial cargo-docking sites during nuclear-cytoplasmic transport (Cullen, 2003;Kohler and Hurt, 2007). Some viruses severely damage NPC architecture, which leads to the inhibition of protein trafficking between the nucleus and the cytoplasm (Belov et al, 2004;Gustin and Sarnow, 2001;Gustin and Sarnow, 2002;Park et al, 2008;Porter and Palmenberg, 2009), inhibition of RNA export from the nucleus (Her et al, 1997;Satterly et al, 2007), and, in some instance, an increase of the nuclear membrane permeability at later times post-infection (Belov et al, 2004;Lidsky et al, 2006). Here, we report that PV 2A pro induces alterations in the NPC, which inhibits nuclear export of U snRNA, rRNA and mRNA but not that of tRNAs.…”

Section: Introductionmentioning

confidence: 99%