Citi Sandra, Guerrera Diego, Spadaro Domenica, Shah Jimit
a Department of Cell Biology ; University of Geneva ; Geneva , Switzerland.
Small GTPases. 2014;5(4):1-15. doi: 10.4161/21541248.2014.973760.
The establishment and maintenance of epithelial cell-cell junctions is crucially important to regulate adhesion, apico-basal polarity and motility of epithelial cells, and ultimately controls the architecture and physiology of epithelial organs. Junctions are supported, shaped and regulated by cytoskeletal filaments, whose dynamic organization and contractility are finely tuned by GTPases of the Rho family, primarily RhoA, Rac1 and Cdc42. Recent research has identified new molecular mechanisms underlying the cross-talk between these GTPases and epithelial junctions. Here we briefly summarize the current knowledge about the organization, molecular evolution and cytoskeletal anchoring of cell-cell junctions, and we comment on the most recent advances in the characterization of the interactions between Rho GTPases and junctional proteins, and their consequences with regards to junction assembly and regulation of cell behavior in vertebrate model systems. The concept of "zonular signalosome" is proposed, which highlights the close functional relationship between proteins of zonular junctions (zonulae occludentes and adhaerentes) and the control of cytoskeletal organization and signaling through Rho GTPases, transcription factors, and their effectors.
上皮细胞间连接的建立和维持对于调节上皮细胞的黏附、顶-基极性和运动性至关重要，最终控制上皮器官的结构和生理功能。连接由细胞骨架丝支撑、塑造和调节，其动态组织和收缩性由Rho家族的GTP酶精细调控，主要是RhoA、Rac1和Cdc42。最近的研究确定了这些GTP酶与上皮连接之间相互作用的新分子机制。在此，我们简要总结了目前关于细胞间连接的组织、分子进化和细胞骨架锚定的知识，并对Rho GTP酶与连接蛋白相互作用的表征及其在脊椎动物模型系统中对连接组装和细胞行为调节的影响方面的最新进展进行评论。我们提出了“带状信号体”的概念，它突出了带状连接（紧密连接和黏着连接）的蛋白质之间的密切功能关系，以及通过Rho GTP酶、转录因子及其效应器对细胞骨架组织和信号传导的控制。
