Recent studies have revealed that cells utilize liquid–liquid phase separation (LLPS) as a mechanism in assembly of membrane-less organelles, such as RNP granules. The nucleus is a well-known membrane-bound organelle surrounded by the nuclear envelope; the nuclear pore complex on the nuclear envelope likely applies LLPS in the central channel to facilitate selective biological macromolecule exchange. Karyopherin-β family proteins exclusively pass through the central channel with cargos by dissolving the phase separated hydrogel formed by the phenylalanine-glycine (FG) repeats-containing nucleoporins. Karyopherin-βs also exhibit dissolution activity for the phase separation of cargo proteins. Many cargos, including RNA-binding proteins containing intrinsically disordered regions (IDRs), undergo phase separation; however, aberrant phase separation is linked to fatal neurodegenerative diseases. Multiple weak interactions between karyopherin-βs and phase separation-prone proteins, such as FG repeats-containing nucleoporins or IDR-containing karyopherin-β cargos, are likely to be important for passing through the nuclear pore complex and maintaining the soluble state of cargo, respectively. In this review, we discuss how karyopherin-βs regulate phase separation to function.

中文翻译：

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Karyopherin-βs 作为相分离调节剂发挥着关键作用

最近的研究表明，细胞利用液-液相分离 (LLPS) 作为无膜细胞器（如 RNP 颗粒）组装的一种机制。细胞核是众所周知的膜结合细胞器，被核膜包围。核膜上的核孔复合物可能在中央通道中应用 LLPS，以促进选择性的生物大分子交换。Karyopherin-β 家族蛋白通过溶解由含有苯丙氨酸-甘氨酸 (FG) 重复序列的核孔蛋白形成的相分离水凝胶，专门通过带有货物的中央通道。Karyopherin-βs 还表现出货物蛋白相分离的溶解活性。许多货物，包括含有内在无序区域 (IDR) 的 RNA 结合蛋白，都经历了相分离；然而，异常相分离与致命的神经退行性疾病有关。karyopherin-βs 和易于相分离的蛋白质之间的多重弱相互作用，例如含有 FG 重复的核孔蛋白或含有 IDR 的 karyopherin-β 货物，对于通过核孔复合物和维持货物的可溶状态可能很重要，分别。在这篇综述中，我们讨论了核转运蛋白-βs 如何调节相分离以发挥作用。