坏死性下垂
雪旺细胞
细胞生物学
生物
平衡
程序性细胞死亡
神经科学
细胞凋亡
遗传学
作者
Mei‐Hwan Wu,Man Li,Lifeng Wei,Minbiao Yan,Li Li,Weichao Ding,Ximing Nian,Wenxiu Dai,Dan Sun,Yucheng Zhu,Qiuying Huang,Xin Lu,Zhiyu Cai,Hong Fan,Xuewen Li,Ling Zhang,Zhixiong Liu,Wei Mo,Xueqin Zhang,Liang Zhang
出处
期刊:Cell Reports
[Elsevier]
日期:2023-07-01
卷期号:42 (7): 112802-112802
被引量:1
标识
DOI:10.1016/j.celrep.2023.112802
摘要
Schwann cells play critical roles in peripheral neuropathies; however, the regulatory mechanisms of their homeostasis remain largely unknown. Here, we show that nucleoporin Seh1, a component of nuclear pore complex, is important for Schwann cell homeostasis. Expression of Seh1 decreases as mice age. Loss of Seh1 leads to activated immune responses and cell necroptosis. Mice with depletion of Seh1 in Schwann cell lineage develop progressive reduction of Schwann cells in sciatic nerves, predominantly non-myelinating Schwann cells, followed by neural fiber degeneration and malfunction of the sensory and motor system. Mechanistically, Seh1 safeguards genome stability by mediating the interaction between SETDB1 and KAP1. The disrupted interaction after ablation of Seh1 derepresses endogenous retroviruses, which triggers ZBP1-dependent necroptosis in Schwann cells. Collectively, our results demonstrate that Seh1 is required for Schwann cell homeostasis by maintaining genome integrity and suggest that decrease of nucleoporins may participate in the pathogenesis of periphery neuropathies.
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