欢迎来到《四川大学学报(医学版)》
罗国文, 周陈晨. 细胞力学蛋白相分离的研究进展[J]. 四川大学学报(医学版), 2024, 55(1): 19-23. DOI: 10.12182/20240160206
引用本文: 罗国文, 周陈晨. 细胞力学蛋白相分离的研究进展[J]. 四川大学学报(医学版), 2024, 55(1): 19-23. DOI: 10.12182/20240160206
LUO Guowen, ZHOU Chenchen. Latest Findings on Phase Separation of Cytomechanical Proteins[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(1): 19-23. DOI: 10.12182/20240160206
Citation: LUO Guowen, ZHOU Chenchen. Latest Findings on Phase Separation of Cytomechanical Proteins[J]. Journal of Sichuan University (Medical Sciences), 2024, 55(1): 19-23. DOI: 10.12182/20240160206

细胞力学蛋白相分离的研究进展

Latest Findings on Phase Separation of Cytomechanical Proteins

  • 摘要: 细胞对力学刺激做出相应的反应很大程度上取决于细胞自身的结构,细胞内丰富的力学蛋白在响应外界力学信号刺激中也起着关键作用。液-液相分离(liquid-liquid phase separation, LLPS)是蛋白质或蛋白质-RNA 复合物自发分离形成两个不同的“相”的过程,即共同存在的低浓度相和高浓度相。研究发现无膜细胞器通过LLPS来形成并维持自身结构,并调节内部的生化活动。LLPS作为一种细胞内调节生物大分子生化反应的新机制,在调控细胞力学蛋白响应中发挥着至关重要的作用。它通过生物大分子之间的多价相互作用形成高浓度的液相凝聚体,进而调控细胞内一系列生命活动。已有研究表明多种细胞力学蛋白通过LLPS响应外界力学信号,进而影响细胞生长、增殖、扩散、迁移、凋亡等生物学行为。除了介绍细胞力学、液-液相分离的发生机制外,本综述还从含 LIM 结构域的蛋白 1(LIM domain-containing protein 1, LIMD1)相分离调控黏着斑成熟和力学信号转导、闭锁小带蛋白(zonula occludens, ZO) 相分离调控细胞间紧密连接、Hippo信号通路的力学蛋白相分离调控细胞增殖和凋亡等方面介绍细胞力学蛋白相分离的最新进展。LLPS的提出不仅解释了细胞内无膜细胞器的形成机制,更为理解细胞内生理或病理的生物学功能提供了新的解题思路。但LLPS驱动黏着斑和细胞边缘动力学的分子机制仍然不完全明了,体外条件下的LLPS能否在机体生理条件下发生仍未明确,通过LLPS解释细胞内多种分子的相互作用仍存在困难,这些方向的研究有待开展。

     

    Abstract: The cellular response to mechanical stimuli depends largely on the structure of the cell itself and the abundance of intracellular cytomechanical proteins also plays a key role in the response to the stimulation of external mechanical signals. Liquid-liquid phase separation (LLPS) is the process by which proteins or protein-RNA complexes spontaneously separate and form two distinct "phases", ie, a low-concentration phase coexisting with a high-concentration phase. According to published findings, membrane-free organelles form and maintain their structures and regulate their internal biochemical activities through LLPS. LLPS, a novel mechanism for intracellular regulation of the biochemical reactions of biomacromolecules, plays a crucial role in modulating the responses of cytomechanical proteins. LLPS leads to the formation of highly concentrated liquid-phase condensates through multivalent interactions between biomacromolecules, thereby regulating a series of intracellular life activities. It has been reported that a variety of cytomechanical proteins respond to external mechanical signals through LLPS, which in turn affects biological behaviors such as cell growth, proliferation, spreading, migration, and apoptosis. Herein, we introduced the mechanisms of cytomechanics and LLPS. In addition, we presented the latest findings on cytomechanical protein phase separation, covering such issues as the regulation of focal adhesion maturation and mechanical signal transduction by LIM domain-containing protein 1 (LIMD1) phase separation, the regulation of intercellular tight junctions by zonula occludens (ZO) phase separation, and the regulation of cell proliferation and apoptosis by cytomechanical protein phase separation of the Hippo signaling pathway. The proposition of LLPS provides an explanation for the formation mechanism of intracellular membraneless organelles and supplies new approaches to understanding the biological functions of intracellular physiology or pathology. However, the molecular mechanisms by which LLPS drives focal adhesions and cell-edge dynamics are still not fully understood. It is not clear whether LLPS under in vitro conditions can occur under physiological conditions of organisms. There are still difficulties to be overcome in using LLPS to explain the interactions of multiple intracellular molecules. Researchers should pursue answers to these questions in the future.

     

/

返回文章
返回