Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins.
Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins.
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DOI：
10.1091/mbc.e13-11-0644
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发表时间：
2014-04
影响因子：
3.3
通讯作者：
Zheng Y
中科院分区：
文献类型：
--
作者：
Guo Y;Kim Y;Shimi T;Goldman RD;Zheng Y
删除所有或不同组合的层蛋白的小鼠细胞用于表明，当表达水平足够高时，层蛋白-A、-B1和-B2中的每一个都可以组装成均匀组织的核层，并确保核孔复合体的均匀分布。相比之下，只有层蛋白-A能保证Emerin的定位。核层(NL)由层蛋白聚合物和与聚合物结合的蛋白质组成。层蛋白和Emerin等NL蛋白的破坏会导致发育缺陷和人类疾病。然而，包括层蛋白-A/C、层蛋白-B_1和层蛋白-B_2在内的多种层蛋白在哺乳动物中的表达为研究核蛋白的组装和功能提供了困难。因此，目前还不清楚不同的板层是否相互依赖以进行适当的NL组装，以及哪些NL功能是所有板层共享的，或者是一个板层所特有的。使用所有或不同组合的Lamin被删除的小鼠细胞，我们证明了每个Lamin组装成NL主要取决于细胞核中存在的lamin浓度。当表达水平足够高时，每个Lamin本身就可以组装成一个均匀组织的NL，这反过来又足以确保核孔复合体的均匀分布。相反，只有层蛋白-A才能确保Emerin在NL中的定位。因此，当研究NL在发育和疾病中的作用时，确定相关Lamin的蛋白质水平以及感兴趣组织中复杂的共有或特定的Lamin功能是至关重要的。
Mouse cells deleted of all or different combinations of lamins are used to show that, when expressed at sufficiently high levels, lamin-A, -B1, and -B2 can each assemble into an evenly organized nuclear lamina and ensure the even distribution of nuclear pore complexes. By contrast, only lamin-A ensures the localization of emerin. 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.