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.

紧密连接和粘附连接是上皮和内皮中细胞间相互作用的专门部位，并参与屏障，粘附和信号传导功能。这些功能由膜和细胞质区室中高度组织的大分子网状结构协调。在这篇综述中，我们讨论了脊椎动物顶端连接的主要胞质支架和衔接子蛋白的结构组织和功能（ZO蛋白，阿法丁，PLEKHA7，环丁菊酯，副环丁菊酯，极性复合蛋白等），着重讨论了它们与细胞骨架和信号蛋白。此外，我们讨论了最近的结果，重点介绍了机械张力，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，以及自发相分离成生物分子缩合物如何促进根尖连接组装。使用基于序列的算法，顶端连接的大部分胞质蛋白被预测为相分离蛋白（PSP），这表明生物分子缩合物的形成是通过聚集蛋白来组织细胞与细胞接触的一般机制。