CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.
J Cell Biochem. 2019 Aug;120(8):13168-13176. doi: 10.1002/jcb.28591. Epub 2019 Mar 19.
Intermediate filaments (IFs) play a key role in the control of cell structure and morphology, cell mechano-responses, migration, proliferation, and apoptosis. However, the mechanisms regulating IFs organization in motile adhesive cells under certain physical/pathological conditions remain to be fully understood. In this study, we found hypo-osmotic-induced stress results in a dramatic but reversible rearrangement of the IF network. Vimentin and nestin IFs are partially depolymerized as they are redistributed throughout the cell cytoplasm after hypo-osmotic shock. This spreading of the IFs requires an intact microtubule network and the motor protein associated transportation. Both nocodazole treatment and depletion of kinesin-1 (KIF5B) block the hypo-osmotic shock-induced rearrangement of IFs showing that the dynamic behavior of IFs largely depends on microtubules and kinesin-dependent transport. Moreover, we show that cell survival rates are dramatically decreased in response to hypo-osmotic shock, which was more severe by vimentin IFs depletion, indicating its contribution to osmotic endurance. Collectively, these results reveal a critical role of vimentin IFs under hypotonic stress and provide evidence that IFs are important for the defense mechanisms during the osmotic challenge.
中间丝（IFs）在控制细胞结构和形态、细胞机械反应、迁移、增殖和凋亡方面起着关键作用。然而，在某些物理/病理条件下，调节运动黏附细胞中 IF 组织的机制仍有待充分理解。在这项研究中，我们发现低渗诱导的应激导致 IF 网络发生剧烈但可逆的重排。低渗休克后，波形蛋白和巢蛋白 IF 部分解聚，重新分布在整个细胞质中。IF 的这种扩散需要完整的微管网络和与运动蛋白相关的运输。长春花碱处理和驱动蛋白-1（KIF5B）耗竭均阻断低渗休克诱导的 IF 重排，表明 IF 的动态行为在很大程度上依赖于微管和驱动蛋白依赖性运输。此外，我们还表明，细胞存活率在低渗冲击下显著下降，而波形蛋白 IF 耗竭时下降更为严重，表明其对渗透压耐受的贡献。总之，这些结果揭示了中间丝在低渗应激下的关键作用，并为 IF 在渗透挑战期间的防御机制中的重要性提供了证据。
