Department of Neurosurgery, Huashan Hospital, the Shanghai Key Laboratory of Medical Epigenetics, Institutes of Biomedical Sciences, State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.
Biochemistry. 2021 Sep 14;60(36):2677-2684. doi: 10.1021/acs.biochem.1c00372. Epub 2021 Aug 11.
Cells are biochemically and morphologically polarized, which allows them to produce different cell shapes for various functions. Remarkably, some polarity protein complexes are asymmetrically recruited and concentrated on limited membrane regions, which is essential for the establishment and maintenance of diverse cell polarity. Though the components and mutual interactions within these protein complexes have been extensively investigated, how these proteins autonomously concentrate at local membranes and whether they have the same organization mechanism in the condensed assembly as that in aqueous solution remain elusive. A number of recent studies suggest that these highly concentrated polarity protein assemblies are membraneless biomolecular condensates which form through liquid-liquid phase separation (LLPS) of specific proteins. In this perspective, we summarize the LLPS-driven condensed protein assemblies found in asymmetric cell division, epithelial cell polarity, and neuronal synapse formation and function. These findings suggest that LLPS may be a general strategy for cells to achieve local condensation of specific proteins, thus establishing cell polarity.
细胞在生化和形态上具有极性,这使它们能够为各种功能产生不同的细胞形状。值得注意的是,一些极性蛋白复合物被不对称地募集并集中在有限的膜区域上,这对于建立和维持不同的细胞极性是至关重要的。尽管这些蛋白复合物的组成和相互作用已经被广泛研究,但这些蛋白如何自主地浓缩在局部膜上,以及它们在浓缩组装中的组织机制是否与在水溶液中的相同,仍然难以捉摸。最近的一些研究表明,这些高度浓缩的极性蛋白组装是无膜的生物分子凝聚物,通过特定蛋白质的液-液相分离(LLPS)形成。在这篇观点文章中,我们总结了在不对称细胞分裂、上皮细胞极性和神经元突触形成和功能中发现的由 LLPS 驱动的凝聚蛋白组装。这些发现表明,LLPS 可能是细胞实现特定蛋白质局部浓缩的一种通用策略,从而建立细胞极性。