The Permeability of Reconstituted Nuclear Pores Provides Direct Evidence for the Selective Phase Model
The Permeability of Reconstituted Nuclear Pores Provides Direct Evidence for the Selective Phase Model
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DOI：
10.1016/j.cell.2012.07.019
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发表时间：
2012-08-17
期刊：
影响因子：
64.5
通讯作者：
Goerlich, Dirk
中科院分区：
文献类型：
--
作者：
Huelsmann, Bastian B.;Labokha, Aksana A.;Goerlich, Dirk
核孔复合物（NPC）通过含FG重复序列的核孔蛋白（NUPS）维持细胞核和细胞质之间的渗透屏障。我们以前提出了一个“选择性阶段模型”，其中FG重复序列相互作用，形成一个筛状屏障，可以通过核转运受体（NTR）的结合局部破坏，但不通过惰性大分子，允许NTR和相关货物的选择性通过。在这里，我们提供了直接的证据，这个模型在生理背景下。通过使用从非洲爪蟾卵提取物重构的NPC，我们表明Nup98对于维持渗透屏障是必不可少的。具体地，需要FG重复之间的多价内聚，包括靠近NPC支架的锚定点的内聚FG重复。我们的数据排除了仅基于FG重复序列和NTR之间相互作用的替代模型，并表明屏障是由筛状FG水凝胶形成的。
Nuclear pore complexes (NPCs) maintain a permeability barrier between the nucleus and the cytoplasm through FG-repeat-containing nucleoporins (Nups). We previously proposed a "selective phase model" in which the FG repeats interact with one another to form a sieve-like barrier that can be locally disrupted by the binding of nuclear transport receptors (NTRs), but not by inert macromolecules, allowing selective passage of NTRs and associated cargo. Here, we provide direct evidence for this model in a physiological context. By using NPCs reconstituted from Xenopus laevis egg extracts, we show that Nup98 is essential for maintaining the permeability barrier. Specifically, the multivalent cohesion between FG repeats is required, including cohesive FG repeats close to the anchorage point to the NPC scaffold. Our data exclude alternative models that are based solely on an interaction between the FG repeats and NTRs and indicate that the barrier is formed by a sieve-like FG hydrogel.