Department of Biochemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
Department of Medicine and Department of Pathology and Cell Biology, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.
J Cell Sci. 2021 Mar 22;134(6):jcs256156. doi: 10.1242/jcs.256156.
The gene encodes the A-type lamins, which polymerize into ∼3.5-nm-thick filaments and, together with B-type lamins and associated proteins, form the nuclear lamina. Mutations in cause a wide variety of pathologies. In this study, we analyzed the nuclear lamina of embryonic fibroblasts from mice, which develop cardiomyopathy and muscular dystrophy. Although the organization of the lamina appeared unaltered, there were changes in chromatin and B-type lamin expression. An increase in nuclear size and consequently a relative reduction in heterochromatin near the lamina allowed for a higher resolution structural analysis of lamin filaments using cryo-electron tomography. This was most apparent when visualizing lamin filaments and using a nuclear extraction protocol. Averaging of individual segments of filaments in mouse fibroblasts resolved two polymers that constitute the mature filaments. Our findings provide better views of the organization of lamin filaments and the effect of a striated muscle disease-causing mutation on nuclear structure.
该基因编码 A 型核纤层蛋白，它们聚合形成约 3.5nm 厚的纤维，并与 B 型核纤层蛋白和相关蛋白一起形成核纤层。基因突变会导致多种病理。在这项研究中，我们分析了患有心肌病和肌肉萎缩症的 小鼠胚胎成纤维细胞的核纤层。尽管核纤层的组织似乎没有改变，但染色质和 B 型核纤层蛋白的表达发生了变化。核的大小增加，因此核纤层附近的异染色质相对减少，这使得使用冷冻电子断层扫描术对核纤层纤维进行更高分辨率的结构分析成为可能。当使用核提取方案可视化核纤层纤维和 时，这种情况最为明显。对 小鼠成纤维细胞中纤维的各个片段进行平均处理，解析出构成成熟纤维的两种聚合物。我们的发现为核纤层纤维的组织以及条纹肌疾病致病突变对核结构的影响提供了更好的观察视角。
