Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis.
Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities in nucleus and cytoplasm. Activation and coordination of the different activities is poorly understood and moreover complicated as some factors translocate between cytoplasm an...
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2013
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oai:doaj.org-article:73acdc6b08794b1f832488c1fc921e9a2021-11-18T06:07:25ZParvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis.1553-73661553-737410.1371/journal.ppat.1003671https://doaj.org/article/73acdc6b08794b1f832488c1fc921e9a2013-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24204256/pdf/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities in nucleus and cytoplasm. Activation and coordination of the different activities is poorly understood and moreover complicated as some factors translocate between cytoplasm and nucleus in preparatory phases. Here we used the ability of parvoviruses to induce nuclear membrane breakdown to understand the triggers of key mitotic enzymes. Nuclear envelope disintegration was shown upon infection, microinjection but also upon their application to permeabilized cells. The latter technique also showed that nuclear envelope disintegration was independent upon soluble cytoplasmic factors. Using time-lapse microscopy, we observed that nuclear disassembly exhibited mitosis-like kinetics and occurred suddenly, implying a catastrophic event irrespective of cell- or type of parvovirus used. Analyzing the order of the processes allowed us to propose a model starting with direct binding of parvoviruses to distinct proteins of the nuclear pore causing structural rearrangement of the parvoviruses. The resulting exposure of domains comprising amphipathic helices was required for nuclear envelope disintegration, which comprised disruption of inner and outer nuclear membrane as shown by electron microscopy. Consistent with Ca⁺⁺ efflux from the lumen between inner and outer nuclear membrane we found that Ca⁺⁺ was essential for nuclear disassembly by activating PKC. PKC activation then triggered activation of cdk-2, which became further activated by caspase-3. Collectively our study shows a unique interaction of a virus with the nuclear envelope, provides evidence that a nuclear pool of executing enzymes is sufficient for nuclear disassembly in quiescent cells, and demonstrates that nuclear disassembly can be uncoupled from initial phases of mitosis.Manvi PorwalSarah CohenKenza SnoussiRuth Popa-WagnerFenja AndersonNathalie Dugot-SenantHarald WodrichChristiane DinsartJürgen A KleinschmidtNelly PantéMichael KannPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 9, Iss 10, p e1003671 (2013) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 |
| spellingShingle |
Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Manvi Porwal Sarah Cohen Kenza Snoussi Ruth Popa-Wagner Fenja Anderson Nathalie Dugot-Senant Harald Wodrich Christiane Dinsart Jürgen A Kleinschmidt Nelly Panté Michael Kann Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. |
| description |
Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities in nucleus and cytoplasm. Activation and coordination of the different activities is poorly understood and moreover complicated as some factors translocate between cytoplasm and nucleus in preparatory phases. Here we used the ability of parvoviruses to induce nuclear membrane breakdown to understand the triggers of key mitotic enzymes. Nuclear envelope disintegration was shown upon infection, microinjection but also upon their application to permeabilized cells. The latter technique also showed that nuclear envelope disintegration was independent upon soluble cytoplasmic factors. Using time-lapse microscopy, we observed that nuclear disassembly exhibited mitosis-like kinetics and occurred suddenly, implying a catastrophic event irrespective of cell- or type of parvovirus used. Analyzing the order of the processes allowed us to propose a model starting with direct binding of parvoviruses to distinct proteins of the nuclear pore causing structural rearrangement of the parvoviruses. The resulting exposure of domains comprising amphipathic helices was required for nuclear envelope disintegration, which comprised disruption of inner and outer nuclear membrane as shown by electron microscopy. Consistent with Ca⁺⁺ efflux from the lumen between inner and outer nuclear membrane we found that Ca⁺⁺ was essential for nuclear disassembly by activating PKC. PKC activation then triggered activation of cdk-2, which became further activated by caspase-3. Collectively our study shows a unique interaction of a virus with the nuclear envelope, provides evidence that a nuclear pool of executing enzymes is sufficient for nuclear disassembly in quiescent cells, and demonstrates that nuclear disassembly can be uncoupled from initial phases of mitosis. |
| format |
article |
| author |
Manvi Porwal Sarah Cohen Kenza Snoussi Ruth Popa-Wagner Fenja Anderson Nathalie Dugot-Senant Harald Wodrich Christiane Dinsart Jürgen A Kleinschmidt Nelly Panté Michael Kann |
| author_facet |
Manvi Porwal Sarah Cohen Kenza Snoussi Ruth Popa-Wagner Fenja Anderson Nathalie Dugot-Senant Harald Wodrich Christiane Dinsart Jürgen A Kleinschmidt Nelly Panté Michael Kann |
| author_sort |
Manvi Porwal |
| title |
Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. |
| title_short |
Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. |
| title_full |
Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. |
| title_fullStr |
Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. |
| title_full_unstemmed |
Parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. |
| title_sort |
parvoviruses cause nuclear envelope breakdown by activating key enzymes of mitosis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2013 |
| url |
https://doaj.org/article/73acdc6b08794b1f832488c1fc921e9a |
| work_keys_str_mv |
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| _version_ |
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