Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK
Wellcome Trust Centre for Cell Biology, Institute of Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
J Cell Sci. 2018 May 1;131(9):jcs213140. doi: 10.1242/jcs.213140.
In metazoa, the Nup107 complex (also known as the nucleoporin Y-complex) plays a major role in formation of the nuclear pore complex in interphase and is localised to kinetochores in mitosis. The Nup107 complex shares a single highly conserved subunit, Seh1 (also known as SEH1L in mammals) with the GATOR2 complex, an essential activator of mTORC1 kinase. mTORC1/GATOR2 has a central role in the coordination of cell growth and proliferation. Here, we use chemical genetics and quantitative chromosome proteomics to study the role of the Seh1 protein in mitosis. Surprisingly, Seh1 is not required for the association of the Nup107 complex with mitotic chromosomes, but it is essential for the association of both the GATOR2 complex and nucleoporin Nup153 with mitotic chromosomes. Our analysis also reveals a role for Seh1 at human centromeres, where it is required for efficient localisation of the chromosomal passenger complex (CPC). Furthermore, this analysis detects a functional interaction between the Nup107 complex and the small kinetochore protein SKAP (also known as KNSTRN).
在后生动物中，Nup107 复合物（也称为核孔蛋白 Y 复合物）在间期核孔复合物的形成中起着重要作用，并在有丝分裂中定位于动粒。Nup107 复合物与 GATOR2 复合物共享一个高度保守的亚基 Seh1（在哺乳动物中也称为 SEH1L），GATOR2 复合物是 mTORC1 激酶的必需激活物。mTORC1/GATOR2 在协调细胞生长和增殖方面起着核心作用。在这里，我们使用化学遗传学和定量染色体蛋白质组学来研究 Seh1 蛋白在有丝分裂中的作用。令人惊讶的是，Seh1 对于 Nup107 复合物与有丝分裂染色体的结合不是必需的，但它对于 GATOR2 复合物和核孔蛋白 Nup153 与有丝分裂染色体的结合是必需的。我们的分析还揭示了 Seh1 在人着丝粒上的作用，在那里它对于染色体乘客复合物（CPC）的有效定位是必需的。此外，该分析检测到 Nup107 复合物与小动粒蛋白 SKAP（也称为 KNSTRN）之间的功能相互作用。
