Department of Neurobiology, Osnabrück, Germany.
Center for Cellular Nanoanalytics, Osnabrück, Germany.
Biol Chem. 2023 Feb 14;404(5):491-498. doi: 10.1515/hsz-2022-0302. Print 2023 Apr 25.
Stress granules are cytosolic, membraneless RNA-protein complexes that form in the cytosol in response to various stressors. Stress granules form through a process termed liquid-liquid phase separation, which increases the local concentration of RNA and protein within the granules, creates dynamic sorting stations for mRNAs and associated proteins, and modulates the availability of mRNA for protein translation. We introduce the concept that neuronal stress granules act as dynamic cytosolic microcompartments in which their components differentially cycle in and out, monitoring the cellular environment. We discuss that neuronal stress granules have distinctive features and contain substructures in which individual components interact transiently. We describe that neuronal stress granules modulate protein expression at multiple levels and affect the proteoform profile of the cytoskeletal protein tau. We argue that a better knowledge of the regulation of stress granule dynamics in neurons and the modulation of their material state is necessary to understand their function during physiological and pathological stress responses. Finally, we delineate approaches to determine the behavior and regulation of critical stress granule organizers and the physical state of stress granules in living neurons.
应激颗粒是细胞溶质无膜的 RNA-蛋白复合物，在各种应激源的作用下在细胞质中形成。应激颗粒通过一种称为液-液相分离的过程形成，该过程增加了颗粒内 RNA 和蛋白质的局部浓度，为 mRNA 和相关蛋白创建动态分拣站，并调节 mRNA 用于蛋白质翻译的可用性。我们提出了神经元应激颗粒作为动态细胞质微区室的概念，其中它们的成分在内外循环中不同，监测细胞环境。我们讨论了神经元应激颗粒具有独特的特征，并包含其中单个成分短暂相互作用的亚结构。我们描述了神经元应激颗粒在多个层面上调节蛋白质表达，并影响细胞骨架蛋白 tau 的蛋白异构体谱。我们认为，更好地了解神经元中应激颗粒动力学的调节及其物质状态的调节，对于理解它们在生理和病理应激反应中的功能是必要的。最后，我们描述了确定关键应激颗粒组织者的行为和调节以及活神经元中应激颗粒的物理状态的方法。
