Department of Biology, Johns Hopkins University, Baltimore, MD 21218 Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218 Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
Mol Biol Cell. 2014 Apr;25(8):1287-97. doi: 10.1091/mbc.E13-11-0644. Epub 2014 Feb 12.
The nuclear lamina (NL) consists of lamin polymers and proteins that bind to the polymers. Disruption of NL proteins such as lamin and emerin leads to developmental defects and human diseases. However, the expression of multiple lamins, including lamin-A/C, lamin-B1, and lamin-B2, in mammals has made it difficult to study the assembly and function of the NL. Consequently, it has been unclear whether different lamins depend on one another for proper NL assembly and which NL functions are shared by all lamins or are specific to one lamin. Using mouse cells deleted of all or different combinations of lamins, we demonstrate that the assembly of each lamin into the NL depends primarily on the lamin concentration present in the nucleus. When expressed at sufficiently high levels, each lamin alone can assemble into an evenly organized NL, which is in turn sufficient to ensure the even distribution of the nuclear pore complexes. By contrast, only lamin-A can ensure the localization of emerin within the NL. Thus, when investigating the role of the NL in development and disease, it is critical to determine the protein levels of relevant lamins and the intricate shared or specific lamin functions in the tissue of interest.
核层（NL）由层粘连蛋白聚合物和与聚合物结合的蛋白质组成。NL 蛋白（如层粘连蛋白和 emerin）的破坏会导致发育缺陷和人类疾病。然而，哺乳动物中多种层粘连蛋白（包括 lamin-A/C、lamin-B1 和 lamin-B2）的表达使得 NL 的组装和功能研究变得困难。因此，尚不清楚不同的层粘连蛋白是否相互依赖于适当的 NL 组装，以及哪些 NL 功能是所有层粘连蛋白共享的，或者是特定于一种层粘连蛋白的。使用去除所有或不同组合层粘连蛋白的小鼠细胞，我们证明了每种层粘连蛋白组装到 NL 中主要取决于核内存在的层粘连蛋白浓度。当以足够高的水平表达时，每种层粘连蛋白都可以单独组装成一个均匀组织的 NL，这反过来又足以确保核孔复合物的均匀分布。相比之下，只有 lamin-A 可以确保 emerin 在 NL 内的定位。因此，在研究 NL 在发育和疾病中的作用时，确定相关层粘连蛋白的蛋白水平以及感兴趣组织中复杂的共享或特定层粘连蛋白功能至关重要。
