Sometimes, holding cells together, even with great strength, is not enough. In epithelia especially, a layer of cells may need to not only hold together but form a complete seal to separate whatever is in contact with the apical side from whatever is in contact with the basal side. That would be a job for The Tight Junction! Well, more accurately, for many tight junctions in an array near the apical surface. Perhaps the best example of the utility of tight junctions is in the digestive tract. The tight junctions that form between cells of the epithelial lining of the gut separate the food and its digestion products from the body at large, forcing macromolecule nutrients to be transported through the epithelial cell by endocytosis/transcytosis to the bloodstream where they can be most efficiently distributed. The tight junctions also form in blood vessels to prevent leakage of blood, and in a variety of organs where liquids must be contained.
Figure 14. Tight Junctions. (A) Tight junctions are usually present in arrays that seal off one side of an epithelial layer from the other multiple times. (B) Each tight junction is formed by very small transmembrane proteins, claudins and occludins, so that the membranes of opposing cells can come into extremely close contact.
An individual tight junction is formed by the interaction of claudins and occludins. They are each 4-pass transmembrane proteins with both N- and C-termini on the cytoplasmic side; the extracellular side has a very low pro le, consisting of one (claudin) or two (occludin) small loops. Because of their small size, when they interact, the membranes are brought together very closely. In order to actually form a seal between cells though, tight junctions must be lined up in close order all the way around the cell, and in fact, usually there are multiple lines, which one could think of as “backup” in case one line develops a leak. Claudin molecules have relatively small cytoplasmic domains and it is not clear whether there are significant interactions with other proteins. However, occludin has a large C-terminal cytoplasmic domain that contains a PDZ-binding domain. PDZ is a protein interaction motif of approximately 80-90 amino acids found in a number of signaling proteins, most often in use to hold signaling complexes near the membrane by interacting with a transmembrane protein, as would be the case here with occludin. These PDZ-containing proteins both have signaling functions and can act as adapters to the cytoskeleton, primarily the actin laments. Finally, although an exact mechanism is unclear, elevated levels of Ca2+, either extracellularly or perimembranously, is associated with tight junction assembly.