Claudin-related intestinal diseases

Enemy at the gates

“…Tight junctions contain a variegated cocktail of proteins, including 24 types of claudins, occludins and junction adhesion molecules (JAMs) [8,9], whose exact composition varies according to the exact location and flux requirements in the organism [9]. In charge of the complex, hay paradoxical task of being both efficient barriers and channels, they monitor and modulate the paracellular flow of water, small solutes and macromolecules, bar the way to invaders but have to let rush through sometimes leukocytes in the middle of diapedesis [5,10,11].…”

“…In charge of the complex, hay paradoxical task of being both efficient barriers and channels, they monitor and modulate the paracellular flow of water, small solutes and macromolecules, bar the way to invaders but have to let rush through sometimes leukocytes in the middle of diapedesis [5,10,11]. Furthermore, at the cell level, junction proteins preserve cell surface polarity and the unique composition of the apical membrane -optimized for facing the harsh exterior conditions as well as for transport and signaling events -by impeding lipid diffusion [9,12]. And finally, the junction complexes represent the central information relay platform between the inside and outside worlds.…”

“…Defective composition or localization of junction complexes take some of the responsibility of diseases linked to fluid absorption and the resulting low grade inflammation, including inflammatory bowel disease (IBD), gallstones and Crohn's disease [9]. And of course, pathogens are having a field day with junction proteins.…”

“…Many pathogens also make their way without much subtlety by damaging tight junction components or entire epithelial cells [5,14]. Some secrete various toxins that dissociate junctional proteins, promote their internalization followed eventually by lysosomal degradation [9,12] or induce apoptosis and cell lysis [14]. Others wash their hands of responsibility and persuade the host cell's matrix metalloproteases (MMPS) to execute the cleavage [8] and some pro-inflammatory cytokines to increase the barrier permeability [5,13].…”

“…Reciprocally, pathogens have at their disposal many means to influence the host genetic expression and signaling networks, like the bacterial type III secretion system effectors, including those governing the expression levels of junction proteins, allowing them to reduce among others the number of fence-forming claudins and increase the channel-forming ones [5,8,12]. The masters of embezzlement are even slikked enough to reposition claudins and occludins into pores leading to uncontrolled calciulm influx and ultimately cell death [9].…”