Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA.
Department of Neuroscience, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA; Howard Hughes Medical Institute at Columbia University, New York, NY 10032, USA; Zuckerman Mind Brain Behavior Institute, Columbia University, New York, NY 10032, USA.
Cell Rep. 2018 Jan 2;22(1):59-71. doi: 10.1016/j.celrep.2017.12.036.
Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins. These and other functions of stress granules facilitate an adaptive cellular response to environmental adversity. A key component of stress granules is the prion-related RNA-binding protein, T cell intracellular antigen-1 (TIA-1). Here, we report that recombinant TIA-1 undergoes rapid multimerization and phase separation in the presence of divalent zinc, which can be reversed by the zinc chelator, TPEN. Similarly, the formation and maintenance of TIA-1-positive stress granules in arsenite-treated cells are inhibited by TPEN. In addition, Zn is released in cells treated with arsenite, before stress granule formation. These findings suggest that Zn is a physiological ligand of TIA-1, acting as a stress-inducible second messenger to promote multimerization of TIA-1 and subsequent localization into stress granules.
应激颗粒是细胞应激时在细胞质中短暂形成的无膜结构，它们通过隔离关键信号转导蛋白来促进非必需 RNA 的翻译抑制，并调节细胞信号转导。应激颗粒的这些和其他功能促进了细胞对环境逆境的适应性反应。应激颗粒的一个关键组成部分是与朊病毒相关的 RNA 结合蛋白 T 细胞内抗原-1（TIA-1）。在这里，我们报告说，重组 TIA-1 在二价锌存在下迅速发生多聚化和相分离，锌螯合剂 TPEN 可以逆转这种多聚化和相分离。类似地，TPEN 抑制亚砷酸盐处理的细胞中 TIA-1 阳性应激颗粒的形成和维持。此外，在形成应激颗粒之前，用亚砷酸盐处理的细胞中释放 Zn。这些发现表明 Zn 是 TIA-1 的生理配体，作为应激诱导的第二信使，促进 TIA-1 的多聚化，随后定位于应激颗粒中。
