Nuclear envelope rupture and NET formation is driven by PKCα-mediated lamin B disassembly

• Verfasst von: Li, Yubin [VerfasserIn]
• Verfasst von: Li, Minghui [VerfasserIn]
• Verfasst von: Weigel, Bettina [VerfasserIn]
• Verfasst von: Mall, Moritz [VerfasserIn]
• Verfasst von: Werth, Victoria P [VerfasserIn]
• Verfasst von: Liu, Ming-Lin [VerfasserIn]
• Titel: Nuclear envelope rupture and NET formation is driven by PKCα-mediated lamin B disassembly
• Verf.angabe: Yubin Li, Minghui Li, Bettina Weigel, Moritz Mall, Victoria P Werth & Ming-Lin Liu
• E-Jahr: 2020
• Jahr: 15 June 2020
• Fussnoten: Gesehen am 18.09.2020
• Titel Quelle: Enthalten in: European Molecular Biology OrganizationEMBO reports
• Ort Quelle: [London] : Nature Publishing Group UK, 2000
• Jahr Quelle: 2020
• Band/Heft Quelle: 21(2020,8) Artikel-Nummer e48779, 19 Seiten
• ISSN Quelle: 1469-3178
• DOI: doi:10.15252/embr.201948779
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: lamin B disassembly
• Sach-SW: NET formation
• Sach-SW: nuclear envelope rupture
• Sach-SW: PKCα
• K10plus-PPN: 1733291822

Abstract

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.