Department of Pathology, the University of Chicago, Illinois 60637, USA.
Ann N Y Acad Sci. 2012 Jun;1257:77-84. doi: 10.1111/j.1749-6632.2012.06528.x.
A principal role of tight junctions is to seal the apical intercellular space and limit paracellular flux of ions and molecules. Despite the fact that tight junctions form heavily cross-linked structures, functional studies have fostered the hypothesis that the tight junction barrier is dynamic and defined by opening and closing events. However, it has been impossible to directly measure tight junction barrier function with sufficient resolution to detect such events. Nevertheless, recent electrophysiological and sieving studies have provided tremendous insight into the presence of at least two pathways of trans-tight junction flux: a high-capacity ion-selective "pore" pathway and a low-capacity "leak" pathway that allows the passage of macromolecules. Furthermore, it is now known that the tight junction molecular structure is highly dynamic and that dynamics are correlated with barrier function. Taken together, these data support a dynamic model of tight junction conductance and suggest that regulation of tight junction openings and closings may provide sensitive means of barrier regulation.
紧密连接的一个主要作用是密封顶端细胞间隙，并限制离子和分子的旁细胞通量。尽管紧密连接形成了高度交联的结构，但功能研究促进了这样一种假设，即紧密连接屏障是动态的，并由开放和关闭事件定义。然而，迄今为止，还不可能以足够高的分辨率直接测量紧密连接屏障功能来检测此类事件。尽管如此，最近的电生理学和筛分研究极大地揭示了至少存在两种跨紧密连接通量的途径：高容量的离子选择性“孔”途径和允许大分子通过的低容量“泄漏”途径。此外，现在已知紧密连接的分子结构具有高度动态性，并且动力学与屏障功能相关。总而言之，这些数据支持紧密连接电导的动态模型，并表明紧密连接开口和闭合的调节可能提供敏感的屏障调节手段。
