Nuclear envelope rupture and NET formation is driven by PKCα-mediated lamin B disassembly
Abstract The nuclear lamina is essential for the structural integration of the nuclear envelope. Nuclear envelope rupture and chromatin externalization is a hallmark of the formation of neutrophil extracellular traps (NETs). NET release was described as a cellular lysis process; however, this notion...
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| Main Authors: | , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
15 June 2020
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| In: |
EMBO reports
Year: 2020, Volume: 21, Issue: 8 |
| ISSN: | 1469-3178 |
| DOI: | 10.15252/embr.201948779 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/embr.201948779 Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/embr.201948779 
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| Author Notes: | Yubin Li, Minghui Li, Bettina Weigel, Moritz Mall, Victoria P Werth & Ming-Lin Liu |
| Summary: | Abstract The nuclear lamina is essential for the structural integration of the nuclear envelope. Nuclear envelope rupture and chromatin externalization is a hallmark of the formation of neutrophil extracellular traps (NETs). NET release was described as a cellular lysis process; however, this notion has been questioned recently. Here, we report that during NET formation, nuclear lamin B is not fragmented by destructive proteolysis, but rather disassembled into intact full-length molecules. Furthermore, we demonstrate that nuclear translocation of PKCα, which serves as the kinase to induce lamin B phosphorylation and disassembly, results in nuclear envelope rupture. Decreasing lamin B phosphorylation by PKCα inhibition, genetic deletion, or by mutating the PKCα consensus sites on lamin B attenuates extracellular trap formation. In addition, strengthening the nuclear envelope by lamin B overexpression attenuates NET release in vivo and reduces levels of NET-associated inflammatory cytokines in UVB-irradiated skin of lamin B transgenic mice. Our findings advance the mechanistic understanding of NET formation by showing that PKCα-mediated lamin B phosphorylation drives nuclear envelope rupture for chromatin release in neutrophils. |
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| Item Description: | Gesehen am 18.09.2020 |
| Physical Description: | Online Resource |
| ISSN: | 1469-3178 |
| DOI: | 10.15252/embr.201948779 |