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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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Hauptverfasser: Li, Yubin (VerfasserIn) , Li, Minghui (VerfasserIn) , Weigel, Bettina (VerfasserIn) , Mall, Moritz (VerfasserIn) , Werth, Victoria P (VerfasserIn) , Liu, Ming-Lin (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 15 June 2020
In: EMBO reports
Year: 2020, Jahrgang: 21, Heft: 8
ISSN:1469-3178
DOI:10.15252/embr.201948779
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.15252/embr.201948779
Verlag, lizenzpflichtig, Volltext: https://www.embopress.org/doi/full/10.15252/embr.201948779
Volltext
Verfasserangaben:Yubin Li, Minghui Li, Bettina Weigel, Moritz Mall, Victoria P Werth & Ming-Lin Liu
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 18.09.2020
Beschreibung:Online Resource
ISSN:1469-3178
DOI:10.15252/embr.201948779

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