The nucleoporin Nup188 controls passage of membrane proteins across the nuclear pore complex.

The nucleoporin Nup188 controls passage of membrane proteins across the nuclear pore complex.
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DOI:
10.1083/jcb.200912045
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发表时间:
2010-06-28
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Antonin W
Antonin W
中科院分区:
其他
文献类型:
--
作者:
Theerthagiri G;Eisenhardt N;Schwarz H;Antonin W

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由于不受限制的蛋白质输入,Nup188-Nup93核孔复合体的耗尽导致细胞核扩大。核膜(NE)的所有运输都是由核孔复合体(NPC)介导的。尽管它们的体积巨大,脊椎动物中的∼60 MD,它们只由∼30不同的蛋白质(核孔蛋白或NUP)组成,其中许多形成亚复合体,作为鼻咽癌组装的基石。其中一个进化保守的亚复合体,Nup93复合体,是连接NPC和NE膜的主要结构成分。利用体外核组装实验,我们证明了Nup93复合体的两个组分Nup188和Nup205对于鼻咽癌的形成是必不可少的。然而,与野生型相比,缺乏Nup188的核的大小增加了几倍。我们证明这种表型是由完整的膜蛋白通过核祖细胞加速移位引起的,这表明Nup188限制了膜蛋白的通过,因此对不同核膜的动态平衡至关重要。
Depletion of the Nup188–Nup93 nuclear pore complex results in enlarged nuclei due to unrestricted protein import. All transport across the nuclear envelope (NE) is mediated by nuclear pore complexes (NPCs). Despite their enormous size, ∼60 MD in vertebrates, they are comprised of only ∼30 distinct proteins (nucleoporins or Nups), many of which form subcomplexes that act as building blocks for NPC assembly. One of these evolutionarily conserved subcomplexes, the Nup93 complex, is a major structural component linking the NPC to the membranes of the NE. Using in vitro nuclear assembly assays, we show that two components of the Nup93 complex, Nup188 and Nup205, are dispensable for NPC formation. However, nuclei lacking Nup188 increase in size by several fold compared with wild type. We demonstrate that this phenotype is caused by an accelerated translocation of integral membrane proteins through NPCs, suggesting that Nup188 confines the passage of membrane proteins and is thus crucial for the homeostasis of the different nuclear membranes.
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