Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.

Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.
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Nup133 是胚胎干细胞中适当的核孔篮组装和动力学所必需的。

DOI:
10.1016/j.celrep.2018.04.070
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发表时间:
2018
期刊:
影响因子:
8.8
通讯作者:
Doye,Valérie
Doye,Valérie
中科院分区:
生物学1区
文献类型:
--
作者:
Souquet,Benoit;Freed,Ellen;Berto,Alessandro;Andric,Vedrana;Audugé,Nicolas;Reina-San-Martin,Bernardo;Lacy,Elizabeth;Doye,Valérie

文献摘要

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Nup 133属于Y-复合物,是核孔复合物(NPC)支架的关键组分。先前对小鼠无效突变的研究表明,Nup 133对胚胎发育至关重要,但对小鼠胚胎干细胞(mESC)增殖无关。使用单孔检测和平均NE-荧光强度,我们发现Nup 133在多能mESCs中用于间期和有丝分裂后NPC支架组装。然而,Nup 133的丢失特别扰乱了核篮的形成,如约一半的NPC中Tpr的缺失与Nup 153的动力学改变相结合所证明的。我们进一步证明,其中央域介导的Nup 133的组装TPR和Nup 153到一个正确配置的核篮子的作用。因此,我们的研究结果重新审视了Y-复合物在孔生物发生中的作用,并深入了解NPC支架结构,核篮组装和NPC之间异质性的产生之间的相互作用。
Nup133 belongs to the Y-complex, a key component of the nuclear pore complex (NPC) scaffold. Studies on a null mutation in mice previously revealed thatNup133is essential for embryonic development but not for mouse embryonic stem cell (mESC) proliferation. Using single-pore detection and average NE-fluorescence intensity, we find that Nup133 is dispensable for interphase and postmitotic NPC scaffold assembly in pluripotent mESCs. However, loss of Nup133 specifically perturbs the formation of the nuclear basket as manifested by the absence of Tpr in about half of the NPCs combined with altered dynamics of Nup153. We further demonstrate that its central domain mediates Nup133's role in assembling Tpr and Nup153 into a properly configured nuclear basket. Our findings thus revisit the role of the Y-complex in pore biogenesis and provide insights into the interplay between NPC scaffold architecture, nuclear basket assembly, and the generation of heterogeneity among NPCs.