Abstract：
Hyperosmotic stress as physiologic dysfunction can reduce the cell volume and then redistribute both protein concentration and ionic strength, but its effect on liquid-liquid phase separation (LLPS) is not well understood. Here, we map the hyperosmotic-stress-induced nuclear LLPS of amyotrophic lateral sclerosis (ALS)-related proteins (fused in sarcoma [FUS], TAR DNA-binding protein 43 [TDP-43]). The dynamic and reversibility of FUS granules are continuable with the increase of hypertonic stimulation time, but those of TDP-43 granules decrease significantly. Strikingly, FUS granules, but not TDP-43 granules, contain essential chaperone Hsp40, which can protect amyloid protein from solid aggregation. Moreover, FUS nuclear granules can co-localize with paraspeckles, but not promyelocytic leukemia (PML) bodies or nuclear speckles, while TDP-43 nuclear granules cannot co-localize with the above nuclear bodies. Together, these results may broaden our understanding of the LLPS of ALS-related proteins in response to cellular stress.
摘要：
高渗应激作为生理功能紊乱可以减少细胞体积，然后重新分配蛋白质浓度和离子强度，但其对液-液相分离（LLPS）的影响尚不清楚。这里,我们绘制了肌萎缩侧索硬化症（ALS）相关蛋白的高渗应激诱导的核LLPS（融合在肉瘤[FUS]中，TARDNA结合蛋白43[TDP-43])。随着高渗刺激时间的增加，FUS颗粒的动态和可逆性是可持续的，但TDP-43颗粒明显减少。引人注目的是，FUS颗粒,但不是TDP-43颗粒,含有必需的分子伴侣Hsp40，可以保护淀粉样蛋白免受固体聚集。此外，FUS核颗粒可以与paraspeckles共同定位，但不是早幼粒细胞白血病（PML）的身体或核斑点，而TDP-43核颗粒不能与上述核体共定位。一起,这些结果可以拓宽我们对ALS相关蛋白对细胞应激的LLPS反应的理解.
