Acute depletion of diacylglycerol from the cis-Golgi affects localized nuclear envelope morphology during mitosis.
Acute depletion of diacylglycerol from the cis-Golgi affects localized nuclear envelope morphology during mitosis.
复制标题
DOI：
10.1194/jlr.m083899
复制
发表时间：
2018-08
影响因子：
6.5
通讯作者：
Larijani B
中科院分区：
文献类型：
--
作者：
Chung GHC;Domart MC;Peddie C;Mantell J;Mclaverty K;Arabiotorre A;Hodgson L;Byrne RD;Verkade P;Arkill K;Collinson LM;Larijani B
核膜（NE）组装失调导致多种癌症；例如，肾癌和某些肺癌是由NE畸形引起的。NE是一个动态的膜室，它在有丝分裂过程中的完成是一个高度调控的过程，但详细的机制仍然不完全清楚。先前的研究发现，分离的含有二酰基甘油（DAG）的囊泡对于完成NE在非体细胞中的融合是必不可少的。我们研究了哺乳动物细胞中顺式高尔基体中DAG缺失对NE重组的影响。利用先进的电子显微镜，我们观察到在终末期哺乳动物细胞NE间隙附近有丰富的DAG囊泡群。我们使用了一个微型单线态氧发生器- c1结构域标签，将富含dag的囊泡定位在核周区域，这表明NE聚变囊泡的存在。我们通过测量重整NE的原位NE边缘曲率来量化高尔基- dag耗竭的影响。与对照组相比，这些细胞的边缘曲率明显减少，这表明NE形态存在局部缺陷。我们的新结果证明了顺式高尔基体中DAG对NE组装的调节作用的重要性。
Dysregulation of nuclear envelope (NE) assembly results in various cancers; for example, renal and some lung carcinomas ensue due to NE malformation. The NE is a dynamic membrane compartment and its completion during mitosis is a highly regulated process, but the detailed mechanism still remains incompletely understood. Previous studies have found that isolated diacylglycerol (DAG)-containing vesicles are essential for completing the fusion of the NE in nonsomatic cells. We investigated the impact of DAG depletion from the cis-Golgi in mammalian cells on NE reassembly. Using advanced electron microscopy, we observed an enriched DAG population of vesicles at the vicinity of the NE gaps of telophase mammalian cells. We applied a mini singlet oxygen generator-C1-domain tag that localized DAG-enriched vesicles at the perinuclear region, which suggested the existence of NE fusogenic vesicles. We quantified the impact of Golgi-DAG depletion by measuring the in situ NE rim curvature of the reforming NE. The rim curvature in these cells was significantly reduced compared with controls, which indicated a localized defect in NE morphology. Our novel results demonstrate the significance of the role of DAG from the cis-Golgi for the regulation of NE assembly.