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Acute depletion of diacylglycerol from the cis-Golgi affects localized nuclear envelope morphology during mitosis

机译:顺式高尔基体中二酰基甘油的急性消耗影响有丝分裂过程中的局部核包膜形态

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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.
机译:核膜(NE)装配失调会导致多种癌症。例如,由于NE畸形而导致肾癌和一些肺癌。 NE是一个动态的膜室,其在有丝分裂过程中的完成是一个高度受控的过程,但其详细机制仍不完全清楚。先前的研究发现,分离的含二酰基甘油(DAG)的囊泡对于在非体细胞中完成NE的融合至关重要。我们研究了哺乳动物细胞中顺式高尔基体中DAG耗竭对NE重组的影响。使用先进的电子显微镜,我们观察到了端粒哺乳动物细胞的NE间隙附近的丰富的DAG囊泡。我们应用了一个微型单线态氧发生器-C1域标签,该标签将富含DAG的囊泡定位在核周区域,这表明NE融合囊泡的存在。我们通过测量重整NE的原位NE边缘曲率来量化高尔基-DAG耗尽的影响。与对照相比,这些细胞的边缘曲率明显降低,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在调节NE组装中的作用。

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