Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 03080, Korea.
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul 03080, Korea.
Cells. 2021 Sep 21;10(9):2493. doi: 10.3390/cells10092493.
Cellular stress induces the formation of membraneless protein condensates in both the nucleus and cytoplasm. The nucleocytoplasmic transport of proteins mainly occurs through nuclear pore complexes (NPCs), whose efficiency is affected by various stress conditions. Here, we report that hyperosmotic stress compartmentalizes nuclear 26S proteasomes into dense nuclear foci, independent of signaling cascades. Most of the proteasome foci were detected between the condensed chromatin mass and inner nuclear membrane. The proteasome-positive puncta were not colocalized with other types of nuclear bodies and were reversibly dispersed when cells were returned to the isotonic medium. The structural integrity of 26S proteasomes in the nucleus was slightly affected under the hyperosmotic condition. We also found that these insulator-body-like proteasome foci were possibly formed through disrupted nucleus-to-cytosol transport, which was mediated by the sequestration of NPC components into osmostress-responding stress granules. These data suggest that phase separation in both the nucleus and cytosol may be a major cell survival mechanism during hyperosmotic stress conditions.
细胞应激会在核和细胞质中诱导无膜蛋白凝聚物的形成。蛋白质的核质转运主要通过核孔复合物（NPC）进行，其效率受各种应激条件的影响。在这里，我们报告渗透压应激会将核 26S 蛋白酶体分隔成密集的核焦点，而不依赖于信号级联。大多数蛋白酶体焦点检测到在浓缩染色质团块和内核膜之间。蛋白酶体阳性的点状结构与其他类型的核体不共定位，并且当细胞返回等渗培养基时可被可逆地分散。在高渗条件下，核内 26S 蛋白酶体的结构完整性受到轻微影响。我们还发现，这些类似于绝缘子体的蛋白酶体焦点可能是通过 NPC 成分被隔离到渗透压响应的应激颗粒中，从而破坏核质转运而形成的。这些数据表明，在渗透压应激条件下，核和细胞质中的相分离可能是细胞主要的生存机制之一。
