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.

中文翻译：

---

核膜破裂和 NET 形成是由 PKCα 介导的核纤层蛋白 B 分解驱动的。

核层对于核膜的结构整合是必不可少的。核膜破裂和染色质外化是中性粒细胞胞外陷阱 (NETs) 形成的标志。NET 发布被描述为细胞裂解过程；然而，这一概念最近受到质疑。在这里，我们报告说，在 NET 形成过程中，核层粘连蛋白 B 不会被破坏性蛋白水解分解，而是分解成完整的全长分子。此外，我们证明了作为激酶诱导核纤层蛋白 B 磷酸化和分解的 PKCα 的核易位导致核膜破裂。通过 PKCα 抑制、基因缺失或通过突变核纤层蛋白 B 上的 PKCα 共有位点来降低核纤层蛋白 B 磷酸化会减弱细胞外陷阱的形成。此外，体内并降低核纤层蛋白 B 转基因小鼠 UVB 照射皮肤中 NET 相关炎性细胞因子的水平。我们的研究结果表明 PKCα 介导的核纤层蛋白 B 磷酸化驱动核膜破裂以释放中性粒细胞中的染色质，从而促进了对 NET 形成的机制理解。