Role of Liquid-Liquid Separation in Endocrine and Living Cells.

Role of Liquid-Liquid Separation in Endocrine and Living Cells.
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DOI:
10.1210/jendso/bvab126
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发表时间:
2021-10-01
影响因子:
4.1
通讯作者:
Fukami M
Fukami M
中科院分区:
其他
文献类型:
--
作者:
Akiba K;Katoh-Fukui Y;Yoshida K;Narumi S;Miyado M;Hasegawa Y;Fukami M

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最近的研究表明,每个真核细胞都含有几个无膜细胞器,这些细胞器是通过液-液相分离(LLP)产生的。LLP是一种物理现象,它瞬时地分隔亚细胞空间,从而促进各种生物反应。LLPs对于细胞功能是不可或缺的;然而,调节异常的LLPs有可能导致不可逆的蛋白质聚集,导致退行性疾病。到目前为止,还没有关于LLP在内分泌学中的作用的系统综述。我们探索了先前关于LLP在活细胞中的作用的研究,特别是从内分泌学的角度。为此,我们在PubMed上筛选了2009至2021年间发表的相关文献,使用与LLP相关的关键字,包括“无膜细胞器”、“相变”和“固有紊乱”,以及内分泌学关键字,如“激素”、“卵巢”、“雄激素”和“糖尿病”。我们还参考了已确定的论文参考清单中的文章。基于从449篇论文中挑选的67篇文章,我们简要概述了目前对活细胞中LLP的理解。然后,我们总结了最近关于LLP在内分泌细胞中的生理或病理作用的文献。LLP在细胞中的发现导致了分子生物学的范式转变。最近的研究表明,LLP通过在睾丸细胞中提供SOX9和CBX2的功能平台来促进男性的性发育。此外,调节失调的LLP与胰腺β细胞中异常的蛋白质聚集有关,从而导致2型糖尿病。尽管如此,我们才刚刚开始了解LLP在内分泌细胞中的重要性。
Recent studies have revealed that every eukaryotic cell contains several membraneless organelles created via liquid–liquid phase separation (LLPS). LLPS is a physical phenomenon that transiently compartmentalizes the subcellular space and thereby facilitates various biological reactions. LLPS is indispensable for cellular functions; however, dysregulated LLPS has the potential to cause irreversible protein aggregation leading to degenerative disorders. To date, there is no systematic review on the role of LLPS in endocrinology. We explored previous studies which addressed roles of LLPS in living cells, particularly from the viewpoint of endocrinology. To this end, we screened relevant literature in PubMed published between 2009 and 2021 using LLPS-associated keywords including “membraneless organelle,” “phase transition,” and “intrinsically disordered,” and endocrinological keywords such as “hormone,” “ovary,” “androgen,” and “diabetes.” We also referred to the articles in the reference lists of identified papers. Based on 67 articles selected from 449 papers, we provided a concise overview of the current understanding of LLPS in living cells. Then, we summarized recent articles documenting the physiological or pathological roles of LLPS in endocrine cells. The discovery of LLPS in cells has resulted in a paradigm shift in molecular biology. Recent studies indicate that LLPS contributes to male sex development by providing a functional platform for SOX9 and CBX2 in testicular cells. In addition, dysregulated LLPS has been implicated in aberrant protein aggregation in pancreatic β-cells, leading to type 2 diabetes. Still, we are just beginning to understand the significance of LLPS in endocrine cells.
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