Alteration of the nuclear pore complex in Ca(2+)-mediated cell death

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2010
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McColl, B.
Bano, Daniele
Dinsdale, David
Cabrera-Socorro, Alfredo
Maida, Simona
Lambacher, Nils
Hengartner, Michael O.
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Cell Death and Differentiation. 2010, 17(1), pp. 119-133. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/cdd.2009.112
Zusammenfassung

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+)] and localization of fluorescent proteins showed that the onset of Ca(2+) 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+)-dependent cell death, including ischemic neuronal demise.

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570 Biowissenschaften, Biologie
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ISO 690MCCOLL, B., Elisa FERRANDO-MAY, Pierluigi NICOTERA, Daniele BANO, David DINSDALE, Alfredo CABRERA-SOCORRO, Simona MAIDA, Nils LAMBACHER, Michael O. HENGARTNER, 2010. Alteration of the nuclear pore complex in Ca(2+)-mediated cell death. In: Cell Death and Differentiation. 2010, 17(1), pp. 119-133. ISSN 1350-9047. eISSN 1476-5403. Available under: doi: 10.1038/cdd.2009.112
BibTex
@article{McColl2010-01Alter-12544,
  year={2010},
  doi={10.1038/cdd.2009.112},
  title={Alteration of the nuclear pore complex in Ca(2+)-mediated cell death},
  number={1},
  volume={17},
  issn={1350-9047},
  journal={Cell Death and Differentiation},
  pages={119--133},
  author={McColl, B. and Ferrando-May, Elisa and Nicotera, Pierluigi and Bano, Daniele and Dinsdale, David and Cabrera-Socorro, Alfredo and Maida, Simona and Lambacher, Nils and Hengartner, Michael O.}
}
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