Nucleocytoplasmic Traffic Disorder Induced by Cardioviruses

Lidsky, Peter V.; Hato, Stanleyson V.; Bardina, Maryana V.; Aminev, Alexei G.; Palmenberg, Ann C.; Sheval, Eugene V.; Polyakov, V. B.; Kuppeveld, Frank J. M. van; Agol, Vadim I.

doi:10.1128/jvi.80.6.2705-2717.2006

Cited by 99 publications

(162 citation statements)

References 82 publications

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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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Section: Discussionmentioning

confidence: 99%

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

et al. 2009

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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%

RNA nuclear export is blocked by poliovirus 2A protease and is concomitant with nucleoporin cleavage

Castelló

Izquierdo

Welnowska

et al. 2009

Journal of Cell Science

102

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“…After release during infection, or as a recombinant protein, the L from EMCV-R (L E ; 67 amino acids [aa]) triggers a cellular phosphorylation cascade aimed at the nucleoporins (Nups), which form the hydrophobic core of nuclear pore complexes (NPC). The degree of Nup hyperphosphorylation is so extensive, and so unlike anything that happens during the normal cell cycle, that it completely disrupts all active host nucleocytoplasmic trafficking pathways (12)(13)(14) (J. Ciomperlik, unpublished results). The altered NPC become open to widespread passive diffusion, allowing essential components to leak from the nucleus and become available for cytoplasmic viral rep-lication.…”

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confidence: 99%