Pan Yi-Yang, Deng Ying, Su Shuai, Yin Jiu-Heng, Chen Yi-Hui, Wang Liu-Can, Sun Li-Hua, Xiao Wei-Dong, Du Guang-Sheng
Department of General Surgery, Xinqiao Hospital, Army Medical University, (Third Military Medical University), Xinqiaozhengjie 183, Shapingba District, Chongqing, 400037, People's Republic of China.
Faculty of Science, University of Waterloo, Waterloo, ON, Canada.
Inflammation. 2023 Feb;46(1):18-34. doi: 10.1007/s10753-022-01724-y. Epub 2022 Sep 1.
Tight junctions (TJs) are located in the apical region of the junctions between epithelial cells and are widely found in organs such as the brain, retina, intestinal epithelium, and endothelial system. As a mechanical barrier of the intestinal mucosa, TJs can not only maintain the integrity of intestinal epithelial cells but also maintain intestinal mucosal permeability by regulating the entry of ions and molecules into paracellular channels. Therefore, the formation disorder or integrity destruction of TJs can induce damage to the intestinal epithelial barrier, ultimately leading to the occurrence of various gastrointestinal diseases, such as inflammatory bowel disease (IBD), gastroesophageal reflux disease (GERD), and irritable bowel syndrome (IBS). However, a large number of studies have shown that TJs protein transport disorder from the endoplasmic reticulum to the apical membrane can lead to TJs formation disorder, in addition to disruption of TJs integrity caused by external pathological factors and reduction of TJs protein synthesis. In this review, we focus on the structural composition of TJs, the formation of clathrin-coated vesicles containing transmembrane TJs from the Golgi apparatus, and the transport process from the Golgi apparatus to the plasma membrane via microtubules and finally fusion with the plasma membrane. At present, the mechanism of the intracellular transport of TJ proteins remains unclear. More studies are needed in the future to focus on the sorting of TJs protein vesicles, regulation of transport processes, and recycling of TJ proteins, etc.
紧密连接(TJs)位于上皮细胞间连接的顶端区域,广泛存在于脑、视网膜、肠上皮和内皮系统等器官中。作为肠黏膜的机械屏障,紧密连接不仅能维持肠上皮细胞的完整性,还可通过调节离子和分子进入细胞旁通道来维持肠黏膜通透性。因此,紧密连接的形成紊乱或完整性破坏可诱发肠上皮屏障损伤,最终导致各种胃肠道疾病的发生,如炎症性肠病(IBD)、胃食管反流病(GERD)和肠易激综合征(IBS)。然而,大量研究表明,除了外部病理因素导致紧密连接完整性破坏以及紧密连接蛋白合成减少外,紧密连接蛋白从内质网到顶端膜的转运紊乱也可导致紧密连接形成紊乱。在本综述中,我们重点关注紧密连接的结构组成、从高尔基体形成含跨膜紧密连接的网格蛋白包被囊泡、通过微管从高尔基体到质膜的转运过程以及最终与质膜融合。目前,紧密连接蛋白的细胞内转运机制仍不清楚。未来需要更多研究关注紧密连接蛋白囊泡的分选、转运过程的调控以及紧密连接蛋白的循环利用等方面。