Karyopherin-βs play a key role as a phase separation regulator.

Karyopherin-βs play a key role as a phase separation regulator.
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Karyopherin-β 作为相分离调节剂发挥着关键作用。

DOI:
10.1093/jb/mvab072
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发表时间:
2021
影响因子:
2.7
通讯作者:
Guo,Lin
Guo,Lin
中科院分区:
生物学4区
文献类型:
--
作者:
Yoshizawa,Takuya;Guo,Lin

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最近的研究表明,细胞利用液-液相分离(LLP)作为组装无膜细胞器的一种机制,如RNP颗粒。细胞核是一个众所周知的被核膜包围的细胞器;核膜上的核孔复合体可能在中央通道中应用LLP,以促进选择性的生物大分子交换。Karyopherin-β家族蛋白通过溶解含有苯丙氨酸-甘氨酸(FG)重复序列的核孔蛋白形成的相分离水凝胶,与货物一起通过中央通道。核黄素-βS对货物蛋白的相分离也表现出溶解活性。许多货物,包括含有固有无序区(IDR)的RNA结合蛋白,经历了相分离;然而,异常的相分离与致命的神经退行性疾病有关。核粘附素-βS与易相分离蛋白之间的多种弱相互作用,如含FG重复序列的核孔蛋白或含IdR的核粘附素-β货物,可能分别对穿透核孔复合体和维持货物的可溶性状态起重要作用。在这篇综述中,我们讨论了核粘附素-βS如何调节相分离的功能。
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.
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