The nucleoporin ELYS/Mel28 regulates nuclear envelope subdomain formation in HeLa cells.

The nucleoporin ELYS/Mel28 regulates nuclear envelope subdomain formation in HeLa cells.
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DOI:
10.4161/nucl.19595
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发表时间:
2012-03-01
期刊:
Nucleus (Austin, Tex.)
影响因子:
--
通讯作者:
Imamoto N
Imamoto N
中科院分区:
其他
文献类型:
--
作者:
Clever M;Funakoshi T;Mimura Y;Takagi M;Imamoto N

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在开放的有丝分裂中,核膜(NE)在每个有丝分裂结束时重新组装。这一过程涉及到核孔复合体(NPC)、核内外膜和核层的改造。在人类细胞中存在细胞周期依赖的NE亚域,其特征是A型富层粘连蛋白/非NPC或B型富层粘连蛋白/鼻咽癌,它们最初分别作为有丝分裂染色体上的核心或非核心区形成。尽管有丝分裂后NE的形成已被广泛研究,但对NPC和NE组装的协调知之甚少。在这里,我们报告了核孔蛋白Elys/Mel28,它是有丝分裂后鼻咽癌形成的关键,对于将Lamin B受体(LBR)招募到染色体非核心区是必不可少的。此外,Elys/Mel28还负责聚焦染色体核心区的A型层粘连蛋白结合蛋白,如Emerin、Lap2α和屏障自整合因子。Elys/Mel28以磷酸化依赖的方式与LBR进行生化相互作用。LBR的募集依赖于核孔蛋白Nup107,Nup107与Elys/Mel28相互作用,而不是与核孔蛋白Pom121相互作用,这表明与Elys/Mel28的特异性分子相互作用参与了NE在非核心区的组装。LBR的缺失既不影响ERERIN的行为,也不影响LAP2α的行为,表明LBR在有丝分裂染色体上的募集并不参与核心区的形成。Elys/Mel28的缺失也加速了Emerin重新进入染色体后进入胞质分裂。我们的数据表明,Elys/Mel28在晚期有丝分裂中NE亚域的形成中发挥了作用。
In open mitosis the nuclear envelope (NE) reassembles at the end of each mitosis. This process involves the reformation of the nuclear pore complex (NPC), the inner and outer nuclear membranes, and the nuclear lamina. In human cells cell cycle-dependent NE subdomains exist, characterized as A-type lamin-rich/NPC-free or B-type lamin-rich/NPC-rich, which are initially formed as core or noncore regions on mitotic chromosomes, respectively. Although postmitotic NE formation has been extensively studied, little is known about the coordination of NPC and NE assembly. Here, we report that the nucleoporin ELYS/Mel28, which is crucial for postmitotic NPC formation, is essential for recruiting the lamin B receptor (LBR) to the chromosomal noncore region. Furthermore, ELYS/Mel28 is responsible for focusing of A-type lamin-binding proteins like emerin, Lap2α and the barrier-to-autointegration factor (BAF) at the chromosomal core region. ELYS/Mel28 biochemically interacts with the LBR in a phosphorylation-dependent manner. Recruitment of the LBR depends on the nucleoporin Nup107, which interacts with ELYS/Mel28 but not on nucleoporin Pom121, suggesting that the specific molecular interactions with ELYS/Mel28 are involved in the NE assembly at the noncore region. The depletion of the LBR affected neither the behavior of emerin nor Lap2α indicating that the recruitment of the LBR to mitotic chromosomes is not involved in formation of the core region. The depletion of ELYS/Mel28 also accelerates the entry into cytokinesis after recruitment of emerin to chromosomes. Our data show that ELYS/Mel28 plays a role in NE subdomain formation in late mitosis.
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