Popoff Michel R, Geny Blandine
Institut Pasteur, Unité des Bactéries anaérobies et Toxines, 75724 Paris cedex151, France.
Biochim Biophys Acta. 2009 Apr;1788(4):797-812. doi: 10.1016/j.bbamem.2009.01.011.
Tight junctions (TJs) and adherens junctions (AJs) are dynamic structures linked to the actin cytoskeleton, which control the paracellular permeability of epithelial and endothelial barriers. TJs and AJs are strictly regulated in a spatio-temporal manner by a complex signaling network, including Rho/Ras-GTPases, which have a pivotal role. Rho preferentially regulates TJs by controlling the contraction of apical acto-myosin filaments, whereas Rac/Cdc42 mainly coordinate the assembly-disassembly of AJ components. However, a subtle balance of Rho/Ras-GTPase activity and interplay between these molecules is required to maintain an optimal organization and function of TJs and AJs. Conversely, integrity of intercellular junctions generates signals through Rho-GTPases, which are involved in the regulation of multiple cellular processes. Rho/Ras-GTPases and the control of intercellular junctions are the target of various bacterial toxins responsible for severe diseases in man and animals, and are part of their mechanism of action. This review focuses on the regulation of TJs and AJs by Rho/Ras-GTPases through molecular approaches and bacterial toxins.
紧密连接（TJs）和黏着连接（AJs）是与肌动蛋白细胞骨架相连的动态结构，它们控制上皮和内皮屏障的细胞旁通透性。紧密连接和黏着连接通过包括Rho/Ras-GTP酶在内的复杂信号网络以时空方式受到严格调控，Rho/Ras-GTP酶起着关键作用。Rho主要通过控制顶端肌动蛋白-肌球蛋白丝的收缩来调节紧密连接，而Rac/Cdc42主要协调黏着连接成分的组装和解聚。然而，需要Rho/Ras-GTP酶活性的微妙平衡以及这些分子之间的相互作用来维持紧密连接和黏着连接的最佳组织和功能。相反，细胞间连接的完整性通过Rho-GTP酶产生信号，这些信号参与多种细胞过程的调节。Rho/Ras-GTP酶和细胞间连接的控制是导致人和动物严重疾病的各种细菌毒素的作用靶点，也是其作用机制的一部分。本综述重点关注Rho/Ras-GTP酶通过分子方法和细菌毒素对紧密连接和黏着连接的调控。
