Tight junction, selective permeability, and related diseases

The tight junction forms a barrier against unlimited paracellular passage but some of the tight junction proteins just do the opposite, they form extracellular channels zigzagging between lateral membranes of neighboring cells. All of these channel-forming proteins and even some of the barrier formers exhibit selectivity, which means that they prefer certain substances over others. All channel formers exhibit at least one of the three types of selectivity: for cations (claudin-2, -10b, -15), for anions (claudin-10a, -17) or for water (claudin-2). Also some, but not all, barrier-forming claudins are charge-selective (claudin-4, -8, -14). Moreover, occludin and tricellulin turned out to be relevant for barrier formation against macromolecule passage. Tight junction proteins are dysregulated or can be genetically defective in numerous diseases, which may lead to three effects: (i) impaired paracellular transport e.g. causing magnesium loss in the kidney, (ii) increased paracellular transport of solutes and water e.g. causing leak-flux diarrhea in the intestine, and (iii) increased permeability to large molecules e.g. unwanted intestinal pathogen uptake fueling inflammatory processes. This review gives an overview on the properties of tight junction proteins featuring selective permeability, and in this context explains how these proteins induce or aggravate diseases.