Medical University of Vienna, Center for Anatomy and Cell Biology, Division of Cell and Developmental Biology, Schwarzspanierstrasse 17, 1090 Vienna, Austria.
Mol Biol Cell. 2022 Dec 1;33(14):ar137. doi: 10.1091/mbc.E22-01-0007. Epub 2022 Oct 6.
Several studies have suggested a role for the LEM-domain protein emerin and the DNA binding factor BAF in nuclear envelope reformation after mitosis, but the exact molecular mechanisms are not understood. Using HeLa cells deficient for emerin or both emerin and lamin A, we show that emerin deficiency induces abnormal aggregation of lamin A at the nuclear periphery in telophase. As a result, nuclear membrane expansion is impaired and BAF accumulates at the core region, the middle part of telophase nuclei. Aggregates do not form when lamin A carries the mutation R435C in the immunoglobulin fold known to prevent interaction of lamin A with BAF suggesting that aggregation is caused by a stabilized association of lamin A with BAF bound to chromosomal DNA. Reintroduction of emerin in the cells prevents formation of lamin A clusters and BAF accumulation at the core region. Therefore emerin is required for the expansion of the nuclear membrane at the core region to enclose the nucleus and for the rapid reformation of the nuclear lamina based on lamin A/C in telophase. Finally, we show that LEM-domain and lumenal domain are required for the targeting of emerin to exert its function at the core region.
已有多项研究表明，LEM 结构域蛋白 emerin 和 DNA 结合因子 BAF 在有丝分裂后核膜重建中发挥作用，但确切的分子机制尚不清楚。本研究使用 HeLa 细胞中缺失 emerin 或 lamin A 的细胞系，发现 emerin 缺失会导致末期核周 lamin A 的异常聚集。结果，核膜扩张受损，BAF 积累在核的核心区域，即末期核的中部。当 lamin A 携带已知可阻止 lamin A 与 BAF 相互作用的免疫球蛋白折叠中的 R435C 突变时，不会形成聚集物，这表明聚集是由与结合在染色体 DNA 上的 BAF 稳定结合的 lamin A 引起的。将 emerin 重新引入细胞中可防止 lamin A 聚集体的形成和 BAF 在核心区域的积累。因此，在末期，emerin 对于核膜在核心区域的扩张以封闭核，以及基于 lamin A/C 的核纤层的快速重建是必需的。最后，我们发现 LEM 结构域和腔结构域对于 emerin 靶向核心区域发挥功能是必需的。
