Department of Gastroenterology, Infectious Diseases, and Rheumatology, Division of Nutritional Medicine, Charité, Universitätsmedizin Berlin, Germany.
Ann N Y Acad Sci. 2012 Jun;1257:1-19. doi: 10.1111/j.1749-6632.2012.06485.x.
The tight junction connects neighboring epithelial or endothelial cells. As a general function, it seals the paracellular pathway and thus prevents back-leakage of just transported solutes and water. However, not all tight junctions are merely tight: some tight junction proteins build their own transport pathways by forming channels selective for small cations, anions, or water. Two families of tight junction proteins have been identified, claudins (27 members in mammals) and tight junction-associated MARVEL proteins ((TAMPs) occludin, tricellulin, and MarvelD3); an additional, structurally different, junction protein is junction adhesion molecule (JAM). Besides classification by genetic or molecular kinship, classification of tight junction proteins has been suggested according to permeability attributes. Recent studies describe specific cis and trans interactions and manifold physiologic regulations of claudins and TAMPs. In many inflammatory and infectious diseases they are found to be altered, for example, causing adversely increased permeability. Currently, attempts are being made to alter the paracellular barrier for therapeutic interventions or for transiently facilitating drug uptake. This overview concludes with a list of open questions and future topics in tight junction research.
紧密连接连接相邻的上皮细胞或内皮细胞。作为一般功能，它封闭了细胞旁途径，从而防止刚刚运输的溶质和水的反向渗漏。然而，并非所有的紧密连接都是仅仅紧密的：一些紧密连接蛋白通过形成选择性的小阳离子、阴离子或水通道来构建自己的运输途径。已经鉴定出两类紧密连接蛋白，claudins（哺乳动物中有 27 个成员）和紧密连接相关的 MARVEL 蛋白（occludin、tricellulin 和 MarvelD3）；另一种结构不同的连接蛋白是连接黏附分子（JAM）。除了根据遗传或分子亲缘关系进行分类外，还根据通透性属性对紧密连接蛋白进行了分类。最近的研究描述了特定的顺式和反式相互作用以及克劳丁和 TAMPs 的多种生理调节。在许多炎症和感染性疾病中，发现它们发生了改变，例如，导致通透性异常增加。目前，人们正试图改变细胞旁屏障以进行治疗干预或暂时促进药物摄取。这篇综述以紧密连接研究中的一系列悬而未决的问题和未来主题作为结束。
