Roles of ZO‐1 and ZO‐2 in Establishment of the Belt‐like Adherens and Tight Junctions with Paracellular Permselective Barrier Function
Roles of ZO‐1 and ZO‐2 in Establishment of the Belt‐like Adherens and Tight Junctions with Paracellular Permselective Barrier Function
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DOI：
10.1111/j.1749-6632.2009.04056.x
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发表时间：
2009-05
影响因子：
5.2
通讯作者：
S. Tsukita;T. Katsuno;Y. Yamazaki;Kazuaki Umeda;A. Tamura;S. Tsukita
中科院分区：
文献类型：
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作者：
S. Tsukita;T. Katsuno;Y. Yamazaki;Kazuaki Umeda;A. Tamura;S. Tsukita
紧密连接（TJ）产生溶质和离子通过细胞旁途径扩散的主要选择性渗透屏障。近年来，TJ的分子结构逐渐被解开，为“屏障学”（由Shoichiro Tsukita定义为多细胞生物中的屏障科学）提供了基础。紧密连接蛋白现在被认为是TJ链的基本组成部分，与其他整合膜蛋白如闭合蛋白、三纤维素、JAM和CAR相关。外周相关的支架蛋白是必需的组织的整体膜蛋白。其中，ZO-1、ZO-2和ZO-3作为TJ组织者引起了极大的关注，因为据报道，ZO-1（在某些情况下，ZO-2/3）与claudins、occludin和JAM以及AF-6/afadin和alpha-catenin直接相关。在这里，我们总结了最近关于小鼠和细胞中ZO-1/2/3-缺陷的研究，这些研究提供了关于ZO-1/2/3在体内功能的明确和重要信息。除了分别抑制ZO-1/2/3的表达外，同时抑制所有三种蛋白质还分别揭示了ZO-1/2和ZO-3在体内的必需和非必需作用。ZO-3以ZO-1/2依赖性方式显示上皮特异性TJ定位。ZO-1和ZO-2在带状粘附连接（zonula adherens）的最终建立中发挥关键作用，随后形成具有细胞旁屏障功能的带状TJ（zonula occludens），从而为上皮和内皮细胞中的选择性细胞旁渗透性提供一般基础。
Tight junctions (TJs) create the primary permselective barrier to diffusion of solutes and ions through the paracellular pathway. The molecular architecture of TJs has gradually been unraveled in recent years, providing the basis for “barriology” (defined by Shoichiro Tsukita as the science of the barrier in multicellular organisms). Claudins are now considered to be the essential basic components of TJ strands, with which other integral membrane proteins, such as occludin, tricellulin, JAMs, and CAR, are associated. Peripherally associated scaffolding proteins are required for the organization of the integral membrane proteins. Among these, ZO‐1, ‐2, and ‐3 have attracted a great deal of attention as TJ organizers, since ZO‐1 (and in some cases, also ZO‐2/3) was reported to be directly associated with claudins, occludin, and JAMs, as well as with AF‐6/afadin and alpha‐catenin. Here we summarize recent studies on ZO‐1/2/3‐deficiency in mice and cells, which have provided clear and important information regarding the functions of ZO‐1/2/3 in vivo. In addition to the respective suppression of ZO‐1/2/3 expression, simultaneous suppression of all three proteins has revealed the essential and nonessential in vivo roles of ZO‐1/2 and ZO‐3, respectively. ZO‐3 shows an epithelial‐specific TJ localization in a ZO‐1/2–dependent fashion. ZO‐1 and ZO‐2 play pivotal roles in the final establishment of the belt‐like adherens junctions (zonula adherens), followed by the formation of the belt‐like TJs (zonula occludens) with paracellular barrier function, thereby providing the general basis for selective paracellular permeability in epithelial and endothelial cells.