A change in nuclear pore complex composition regulates cell differentiation.
A change in nuclear pore complex composition regulates cell differentiation.
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DOI：
10.1016/j.devcel.2011.11.021
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发表时间：
2012-02-14
影响因子：
11.8
通讯作者：
Hetzer, Martin W.
中科院分区：
文献类型：
--
作者：
D'Angelo, Maximilian A.;Gomez-Cavazos, J. Sebastian;Mei, Arianna;Lackner, Daniel H.;Hetzer, Martin W.
核孔复合物（NPC）由大约30种不同的蛋白质组成，称为核孔蛋白。先前的研究表明，几种Nup表现出细胞类型特异性表达，并且NPC组分中的突变导致组织特异性疾病。在这里，我们表明，一个特定的NPC组成的变化是需要肌源性和神经元分化。跨膜核孔蛋白Nup210在增殖的成肌细胞和胚胎干细胞中不存在，但在细胞分化过程中表达并掺入NPC中。通过RNAi阻止Nup210的产生阻断了肌生成和ES细胞向神经祖细胞的分化。我们发现，Nup210添加到NPC不影响核运输，但需要诱导细胞分化所必需的基因。我们的研究结果确定了NPC组成的单一变化是细胞分化的重要步骤，并确定了Nup210在基因表达调控和细胞命运决定中的作用。
Nuclear pore complexes (NPCs) are built from ~30 different proteins called nucleoporins. Previous studies have shown that several Nups exhibit cell-type-specific expression and that mutations in NPC components result in tissue-specific diseases. Here we show that a specific change in NPC composition is required for both myogenic and neuronal differentiation. The transmembrane nucleoporin Nup210 is absent in proliferating myoblasts and embryonic stem (ES) cells but becomes expressed and incorporated into NPCs during cell differentiation. Preventing Nup210 production by RNAi blocks myogenesis and the differentiation of ES cells into neuroprogenitors. We found that the addition of Nup210 to NPCs does not affect nuclear transport but is required for the induction of genes that are essential for cell differentiation. Our results identify a single change in NPC composition as an essential step in cell differentiation and establish a role for Nup210 in gene expression regulation and cell fate determination.
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