The Molecular Basis for the Structure, Function, and Regulation of Tight Junctions

Abstract

Publisher Summary Tight Junctions (TJ) are the most apical element of the junctional complex of polarized epithelial cells, which also comprises zonulae adhaerentes and desmosomes. TJ are also present in capillary endothelial cells (ECs) (blood-tissue barriers) and in other specialized cell types, such as Sertoli cells. The ultrastructure of TJ is characteristic. By transmission electron microscopy, TJ appear as a series of very close appositions of the external leaflets of adjacent membranes. The main function of TJ is to form a gasket-like, semipermeable barrier that prevents the free diffusion of ions, molecules, and cells across the space between epithelial cells (paracellular pathway). The barrier function allows epithelial and endothelial cell sheets to maintain the physiological gradients of solutes (ions, nutrients, secretory products, etc.) across different body compartments, a function that is critical for tissues involved in polarized absorption and secretion. In addition, the TJ barrier allows the formation of specialized environments where immune cells, antigens, and antibodies are sequestered. The permeability of TJ to ions and small molecules can be determined in cultured cells by the measurement of electrical resistance and tracer fluxes and can be determined in intact tissues and organs by labeled or electron-dense tracer studies. TJ respond to hormones, growth factors, cytokines, neuronal influences, and osmotic and mechanical stress. To understand the molecular basis for the heterogeneity and modulation of TJ, it is necessary to determine their protein composition in different tissues and to study how different factors affect their organization.