Tight junction interactions

Tight junctions (TJs) are the most apical component of the epithelial junctional complex forming a belt-like structure at the cellular junction. When visualized by freeze-fracture electron microscopy they appear as a branched network of intramembrane strands that correspond to the sites of direct membrane contacts and that are composed of the integral membrane claudin proteins. The TJs act as a primary barrier to the diffusion of solutes through the paracellular space (barrier function) (Tsukita et al., 2001). They also prevent the intermixing of intramembrane proteins and lipids and thus create a boundary between the apical and the basolateral membrane domains of polarized epithelial cells (fence function) (Tsukita et al., 2001). Interestingly, the fence function seems not to depend on TJ strands (Umeda et al., 2006). Recents evidence indicates that the TJs also participate in signal transduction mechanisms which regulate cell proliferation and morphogenesis (Matter and Balda, 2003; Matter and Balda, 2007). This module describes the major molecular interactions responsible for the formation of TJ strands and for the rectruitment of the PAR-3-PKC-PAR-6 and CRB3-Pals1-PATJ complexes that function in tight junction formation (Ebnet, 2008).

紧密连接（TJs）是构成上皮连接复合体最顶端的组分，在细胞连接处形成一环状结构。通过冷冻断裂电子显微镜观察，它们呈现为膜内丝状分支网络，对应于直接膜接触的位点，并由整合膜蛋白钙粘蛋白组成。紧密连接作为防止溶质通过细胞间空间的初级屏障（屏障功能）（Tsukita 等人，2001年）。此外，它们还能阻止膜内蛋白和脂质的混合，从而在极化上皮细胞的顶端和基底侧膜域之间建立边界（围栏功能）（Tsukita 等人，2001年）。有趣的是，围栏功能似乎并不依赖于紧密连接的丝状结构（Umeda 等人，2006年）。近期证据表明，紧密连接还参与信号转导机制，这些机制调节细胞增殖和形态发生（Matter 和 Balda，2003年；Matter 和 Balda，2007年）。本模块描述了负责紧密连接丝状结构形成以及PAR-3-PKC-PAR-6 和 CRB3-Pals1-PATJ 复合物招募的主要分子相互作用，这些复合物在紧密连接形成中发挥作用（Ebnet，2008年）。