期刊
EMBO REPORTS
卷 21, 期 8, 页码 -出版社
WILEY
DOI: 10.15252/embr.201948779
关键词
lamin B disassembly; NET formation; nuclear envelope rupture; PKC alpha
资金
- Lupus Research Alliance [416805]
- NIH [R21AI144838]
- Veterans Affairs Merit Review Award
- ERC StG [804710]
- Hector Stiftung II gGmbH
- Helmholtz International Graduate School Fellowship
- European Research Council (ERC) [804710] Funding Source: European Research Council (ERC)
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 PKC alpha, which serves as the kinase to induce lamin B phosphorylation and disassembly, results in nuclear envelope rupture. Decreasing lamin B phosphorylation by PKC alpha inhibition, genetic deletion, or by mutating the PKC alpha consensus sites on lamin B attenuates extracellular trap formation. In addition, strengthening the nuclear envelope by lamin B overexpression attenuates NET releasein vivoand 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 PKC alpha-mediated lamin B phosphorylation drives nuclear envelope rupture for chromatin release in neutrophils.
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