The claudin protein family has many members (24 in humans), and these are expressed in different combinations in different epithelia to confer particular permeability properties on the epithelial sheet. They are thought to form paracellular pores—selective channels allowing specific ions to cross the tight-junctional barrier, from one extracellular space to another. A specific claudin found in kidney epithelial cells, for example, is needed to let Mg2+ pass between the cells of the kidney tubules so that this ion can be resorbed from the urine into the blood. A mutation in the gene encoding this claudin results in excessive loss of Mg2+ in the urine.
Like the cadherin molecules of an adherens junction, the claudins and occludins of a tight junction interact with each other on their extracellular sides to promote junction assembly. Also as in adherens junctions, the organization of adhesion proteins in a tight junction depends on additional proteins that bind the cytoplasmic side of the adhesion proteins. The key organizational proteins at tight junctions are the zonula occludens (ZO) proteins. The three major members of the ZO family—ZO-1, ZO-2, and ZO-3—are large scaffold proteins that provide a structural support on which the tight junction is built. These intracellular molecules cell cell 0.3 µm 12 consist of strings of protein-binding domains, typically including several PDZ domains—segments about 80 amino acids long that can recognize and bind the C-terminal tails of specific partner proteins (Figure 19–22). One domain of these scaffold proteins can attach to a claudin protein, while others can attach to occludin or the actin cytoskeleton. Moreover, one molecule of scaffold protein can bind to another. In this way, the cell can assemble a mat of intracellular proteins that organizes and positions the sealing strands of the tight junction.
The tight-junctional network of sealing strands usually lies just apical to adherens and desmosome junctions that bond the cells together mechanically; the whole assembly is called a junctional complex (see Figure 19–2). The parts of this junctional complex depend on each other for their formation. For example, anticadherin antibodies that block the formation of adherens junctions also block the formation of tight junctions.
Tight junctions block the passageways through the gaps between epithelial cells, preventing extracellular molecules from leaking from one side of an epithelium to the other. Another type of junctional structure has a radically different function: it bridges gaps between adjacent cells so as to create direct channels from the
Figure 19–21 A model of a tight junction.
(a) the sealing strands hold adjacent plasma membranes together. the strands are composed of transmembrane proteins that make contact across the intercellular space and create a seal. (B) the molecular composition of a sealing strand. the major extracellular components of the tight junction are members of a family of proteins with four transmembrane domains. One of these proteins, claudin, is the most important for the assembly and structure of the sealing strands, whereas the related protein occludin has the less critical role of determining junction permeability. the two termini of these proteins are both on the cytoplasmic side of the membrane, where they interact with large scaffolding proteins that organize the sealing strands and link the tight junction to the actin cytoskeleton (not shown here, but see Figure 19–22).