Details

Autor(en) / Beteiligte

• Li, Yubin
• Li, Minghui
• Weigel, Bettina
• Mall, Moritz
• Werth, Victoria P
• Liu, Ming‐Lin

Titel

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

Ist Teil von

• EMBO reports, 2020-08, Vol.21 (8), p.e48779-n/a

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2020

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• 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. Synopsis Nuclear envelope rupture is crucial for chromatin externalization during NET formation. Nuclear lamin B disassembly, but not cleavage, regulated by PKCα‐mediated phosphorylation, is responsible for nuclear envelope rupture and NET release. Lamin B disassembly is responsible for nuclear envelope rupture and chromatin release during NET formation. Nuclear lamin B disassembly is regulated by PKCα‐mediated lamin B phosphorylation. Strengthening the nuclear envelope by lamin B overexpression attenuates NET formation. Nuclear envelope rupture is crucial for chromatin externalization during NET formation. Nuclear lamin B disassembly, but not cleavage, regulated by PKCα‐mediated phosphorylation, is responsible for nuclear envelope rupture and NET release.