Nuclear envelope rupture and NET formation is driven by PKCα‐mediated lamin B disassembly. (15th June 2020)

• Record Type: Journal Article
• Authors: Li, Yubin; Li, Minghui; Weigel, Bettina; Mall, Moritz; Werth, Victoria P; Liu, Ming‐Lin
• Is Part Of: EMBO reports. Volume 21:Number 8(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-06-15
• Subjects: lamin B disassembly -- NET formation -- nuclear envelope rupture -- PKCα; Molecular biology -- Periodicals; Molecular Biology -- Periodicals; Molecular biology; Periodicals; 572.8
• DOI: 10.15252/embr.201948779
• Languages: English
• ISSNs: 1469-221X

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. 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. Abstract : 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.