Department of Cell Biology, Faculty of Sciences, University of Geneva, 4 Boulevard d'Yvoy, CH-1211 Geneva, Switzerland.
Department of Cell Biology, Faculty of Sciences, University of Geneva, 4 Boulevard d'Yvoy, CH-1211 Geneva, Switzerland.
Biochim Biophys Acta Biomembr. 2020 Oct 1;1862(10):183399. doi: 10.1016/j.bbamem.2020.183399. Epub 2020 Jun 15.
Tight and adherens junctions are specialized sites of cell-cell interaction in epithelia and endothelia, and are involved in barrier, adhesion, and signaling functions. These functions are orchestrated by a highly organized meshwork of macromolecules in the membrane and cytoplasmic compartments. In this review, we discuss the structural organization and functions of the major cytoplasmic scaffolding and adaptor proteins of vertebrate apical junctions (ZO proteins, afadin, PLEKHA7, cingulin, paracingulin, polarity complex proteins, and a few others), focusing on their interactions with cytoskeletal and signaling proteins. Furthermore, we discuss recent results highlighting how mechanical tension, protein-protein interactions and post-translational modifications regulate the conformation and function of scaffolding proteins, and how spontaneous phase separation into biomolecular condensates contributes to apical junction assembly. Using a sequence-based algorithm, a large fraction of cytoplasmic proteins of apical junctions are predicted to be phase separating proteins (PSPs), suggesting that formation of biomolecular condensates is a general mechanism to organize cell-cell contacts by clustering proteins.
紧密连接和黏附连接是上皮细胞和内皮细胞中细胞-细胞相互作用的特化部位，参与屏障、黏附和信号转导功能。这些功能是由膜和细胞质区室中高度组织的大分子网格来协调的。在这篇综述中，我们讨论了脊椎动物顶端连接（ZO 蛋白、afadin、PLEKHA7、cingulin、paracingulin、极性复合物蛋白和其他一些蛋白）的主要细胞质支架和衔接蛋白的结构组织和功能，重点讨论了它们与细胞骨架和信号蛋白的相互作用。此外，我们还讨论了最近的研究结果，这些结果强调了机械张力、蛋白质-蛋白质相互作用和翻译后修饰如何调节支架蛋白的构象和功能，以及生物分子凝聚物的自发相分离如何有助于顶端连接的组装。使用基于序列的算法，预测顶端连接的细胞质蛋白中有很大一部分是相分离蛋白（PSP），这表明生物分子凝聚物的形成是通过聚集蛋白质来组织细胞-细胞接触的一般机制。
