Fukuhara Atsunori, Irie Kenji, Yamada Akio, Katata Tatsuo, Honda Tomoyuki, Shimizu Kazuya, Nakanishi Hiroyuki, Takai Yoshimi
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Genes Cells. 2002 Oct;7(10):1059-72. doi: 10.1046/j.1365-2443.2002.00578.x.
In polarized epithelial cells, cell-cell adhesion forms specialized membrane structures comprised of claudin-based tight junctions (TJs) and of E-cadherin-based adherens junctions (AJs). These structures are aligned from the apical to the basal side of the lateral membrane, but the mechanism of this organization remains unknown. Nectin is a Ca2+ independent immunoglobulin-like cell-cell adhesion molecule which localizes at AJs. Nectin is associated with E-cadherin through their respective cytoplasmic tail-binding proteins, afadin and catenins, and involved in the formation of AJs in cooperation with E-cadherin. We show here that nectin is also involved in the formation of TJs.
During the formation of the junctional complex consisting of AJs and TJs in Madin-Darby canine kidney (MDCK) cells, claudin and occludin accumulated at the apical sites of the nectin-based cell-cell adhesion sites. This accumulation of claudin and occludin was inhibited by inhibitors acting on the trans interaction of nectin. The barrier function of TJs was also impaired by the nectin inhibitors. It has been shown that a phorbol ester promotes the formation of a TJ-like structure in an E-cadherin-independent manner. This phorbol ester-induced formation of the TJ-like structure was also inhibited by the nectin inhibitors.
These results suggest a role of the nectin-afadin system in the organization of TJs as well as AJs in epithelial cells.
在极化上皮细胞中，细胞间黏附形成了由紧密连接蛋白构成的紧密连接（TJs）和E-钙黏蛋白构成的黏着连接（AJs）组成的特殊膜结构。这些结构沿侧膜从顶端向基底侧排列，但其组织机制尚不清楚。Nectin是一种不依赖Ca2+的免疫球蛋白样细胞间黏附分子，定位于AJs。Nectin通过其各自的胞质尾结合蛋白afadin和连环蛋白与E-钙黏蛋白相关联，并与E-钙黏蛋白协同参与AJs的形成。我们在此表明，Nectin也参与紧密连接的形成。
在Madin-Darby犬肾（MDCK）细胞中由AJs和TJs组成的连接复合体形成过程中，紧密连接蛋白和闭合蛋白在基于Nectin的细胞间黏附位点的顶端部位积累。作用于Nectin反式相互作用的抑制剂可抑制紧密连接蛋白和闭合蛋白的这种积累。Nectin抑制剂也损害了紧密连接的屏障功能。已经表明，佛波酯以不依赖E-钙黏蛋白的方式促进类紧密连接结构的形成。这种佛波酯诱导的类紧密连接结构的形成也受到Nectin抑制剂的抑制。
这些结果表明Nectin-afadin系统在上皮细胞紧密连接以及黏着连接的组织中发挥作用。
