Furuse Mikio
Division of Cell Biology, Kobe University Graduate School of Medicine.
Yakugaku Zasshi. 2014;134(5):615-21. doi: 10.1248/yakushi.14-00006-1.
Within an epithelial cellular sheet, the paracellular pathway can be divided into two routes: one between two adjacent cells and one at tricellular contacts, where the vertices of three cells meet. For epithelial barrier function, tight junctions restrict solute permeability through the paracellular pathway between two cells, while tricellular contacts contain specialized structures of tight junctions, named tricellular tight junctions (tTJs). Two types of membrane proteins, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1 and angulin-3/ILDR2) have been identified as molecular components of tTJs. Angulins recruit triellulin to tTJs and these tTJ-associated proteins are required for normal tTJ formation as well as strong epithelial barrier function. Furthermore, mutations in tricellulin and angulin-2/ILDR1 genes cause autosomal recessive familial deafness, DFNB49 and DFNB42, respectively. Further analyses of the angulin-tricellulin system should lead to better understanding of the molecular mechanism and regulation of tTJs.
在上皮细胞层内,细胞旁途径可分为两条路线:一条位于两个相邻细胞之间,另一条位于三细胞接触处,即三个细胞的顶点交汇之处。对于上皮屏障功能而言,紧密连接限制溶质通过两个细胞之间的细胞旁途径的通透性,而三细胞接触处包含紧密连接的特殊结构,称为三细胞紧密连接(tTJs)。两种膜蛋白,即三细胞素和angulin家族蛋白(angulin-1/LSR、angulin-2/ILDR1和angulin-3/ILDR2)已被确定为tTJs的分子成分。Angulins将三细胞素招募至tTJs,这些与tTJ相关的蛋白对于正常tTJ的形成以及强大的上皮屏障功能是必需的。此外,三细胞素和angulin-2/ILDR1基因的突变分别导致常染色体隐性遗传性耳聋DFNB49和DFNB42。对angulin-三细胞素系统的进一步分析应能更好地理解tTJs的分子机制和调控。