Yoshizawa Takuya, Matsumura Hiroyoshi
College of Life Sciences, Ritsumeikan University, Kusatsu, Shiga 525-8577, Japan.
Biophys Physicobiol. 2020 Feb 20;17:25-29. doi: 10.2142/biophysico.BSJ-2019052. eCollection 2020.
Low-complexity (LC) sequences, regions that are predominantly made up of limited amino acids, are often observed in eukaryotic nuclear proteins. The role of these LC sequences has remained unclear for decades. Recent studies have shown that LC sequences are important in the formation of membrane-less organelles via liquid-liquid phase separation (LLPS). The RNA binding protein, fused in sarcoma (FUS), is the most widely studied of the proteins that undergo LLPS. It forms droplets, fibers, or hydrogels using its LC sequences. The N-terminal LC sequence of FUS is made up of Ser, Tyr, Gly, and Gln, which form a labile cross-β polymer core while the C-terminal Arg-Gly-Gly repeats accelerate LLPS. Normally, FUS localizes to the nucleus via the nuclear import receptor karyopherin β2 (Kapβ2) with the help of its C-terminal proline-tyrosine nuclear localization signal (PY-NLS). Recent findings revealed that Kapβ2 blocks FUS mediated LLPS, suggesting that Kapβ2 is not only a transport protein but also a chaperone which regulates LLPS during the formation of membrane-less organelles. In this review, we discuss the effects of the nuclear import receptors on LLPS.
低复杂性（LC）序列，即主要由有限数量氨基酸组成的区域，在真核细胞核蛋白中经常被观察到。几十年来，这些LC序列的作用一直不清楚。最近的研究表明，LC序列在通过液-液相分离（LLPS）形成无膜细胞器的过程中很重要。RNA结合蛋白，肉瘤融合蛋白（FUS），是经历LLPS的蛋白质中研究最广泛的。它利用其LC序列形成液滴、纤维或水凝胶。FUS的N端LC序列由Ser、Tyr、Gly和Gln组成，它们形成一个不稳定的交叉β聚合物核心，而C端的Arg-Gly-Gly重复序列加速LLPS。正常情况下，FUS在其C端脯氨酸-酪氨酸核定位信号（PY-NLS）的帮助下，通过核输入受体核转运蛋白β2（Kapβ2）定位于细胞核。最近的研究结果表明，Kapβ2阻断FUS介导的LLPS，这表明Kapβ2不仅是一种转运蛋白，而且是一种伴侣蛋白，在无膜细胞器形成过程中调节LLPS。在这篇综述中，我们讨论了核输入受体对LLPS的影响。
