液-液相分离在发育性疾病中的研究进展

Progress and prospects of liquid-liquid phase separation in developmental diseases

真核细胞内存在膜结合细胞器以及无膜区室,它们将细胞核和细胞质分成不同的亚区域并允许特定的生化反应发生。膜结合细胞器的生理机制已经被广泛表征,但是无膜区室的形成和功能尚未被研究透彻。过去10年,关于液-液相分离(LLPS)在无膜细胞器形成过程中的作用研究取得了重大进展。LLPS作为细胞生化反应的聚集分离机制,与信号传导、基因转录调控等多种生理过程相关,而异常的LLPS可能会导致发育性疾病的发生。本综述讨论了LLPS的发生机制以及异常LLPS与发育性疾病关系的最新进展,并讨论了这些进展如何为开发基于LLPS的治疗手段提供帮助。

Membrane-bound organelles as well as membrane-free compartments exist in eukaryotic cells,which divide the nucleus and cytoplasm into distinct subregions and allow specific biochemical reactions to occur.The physiological mechanisms of membrane-bound organelles have been extensively characterized,but the formation and function of membrane-free compartments have not been thoroughly studied.Over the past decade,significant progress had been made in the studies about the role of liquid-liquid phase separation(LLPS)in the formation of membrane-free organelles.LLPS which serves as an aggregated separation mechanism for cellular biochemical reactions,is associated with a variety of physiological processes such as signal transduction and gene transcriptional regulation;while aberrant LLPS may contribute to the occurrence of developmental diseases.The present review investigates the role of LLPS as a mechanism of aggregation and segregation of cellular biochemical responses.The mechanisms of LLPS development and recent advances in the relationships between aberrant LLPS and developmental diseases are forward discussed,as well as how these advances may aid in the development of LLPS-based therapies.