Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, 10595, USA; Department of Medicine, New York Medical College, Valhalla, NY, 10595, USA.
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY, 10595, USA.
Anal Biochem. 2020 May 15;597:113691. doi: 10.1016/j.ab.2020.113691. Epub 2020 Mar 16.
Membraneless organelles (MLOs) in the cytoplasm and nucleus in the form of 2D and 3D phase-separated biomolecular condensates are increasingly viewed as critical in regulating diverse cellular functions. These functions include cell signaling, immune synapse function, nuclear transcription, RNA splicing and processing, mRNA storage and translation, virus replication and maturation, antiviral mechanisms, DNA sensing, synaptic transmission, protein turnover and mitosis. Components comprising MLOs often associate with low affinity; thus cell integrity can be critical to the maintenance of the full complement of respective MLO components. Phase-separated condensates are typically metastable (shape-changing) and can undergo dramatic, rapid and reversible assembly and disassembly in response to cell signaling events, cell stress, during mitosis, and after changes in cytoplasmic "crowding" (as observed with condensates of the human myxovirus resistance protein MxA). Increasing evidence suggests that neuron-specific aberrations in phase-separation properties of RNA-binding proteins (e.g. FUS and TDP-43) and others (such as the microtubule-binding protein tau) contribute to the development of degenerative neurological diseases (e.g. amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and Alzheimer's disease). Thus, studies of liquid-like phase separation (LLPS) and the formation, structure and function of MLOs are of considerable importance in understanding basic cell biology and the pathogenesis of human diseases.
无膜细胞器 (MLOs) 以 2D 和 3D 相分离生物分子凝聚体的形式存在于细胞质和细胞核中，它们在调节多种细胞功能方面的作用正受到越来越多的关注。这些功能包括细胞信号转导、免疫突触功能、核转录、RNA 剪接和加工、mRNA 储存和翻译、病毒复制和成熟、抗病毒机制、DNA 感应、突触传递、蛋白质周转和有丝分裂。组成 MLO 的成分通常以低亲和力结合；因此，细胞完整性对于维持完整的 MLO 成分至关重要。相分离凝聚体通常是亚稳态的（形状变化），可以在细胞信号事件、细胞应激、有丝分裂期间以及细胞质“拥挤”变化后，发生剧烈、快速和可逆的组装和拆卸（如观察到人巨细胞病毒抗性蛋白 MxA 的凝聚体）。越来越多的证据表明，RNA 结合蛋白（如 FUS 和 TDP-43）和其他蛋白（如微管结合蛋白 tau）的相分离特性在神经元中的异常与退行性神经疾病（如肌萎缩性侧索硬化症、额颞叶痴呆和阿尔茨海默病）的发展有关。因此，研究液态相分离 (LLPS) 和 MLO 的形成、结构和功能对于理解基础细胞生物学和人类疾病的发病机制具有重要意义。
