Observations of different kinds of epithelia reveal that the complexity and number of strands forming the zonulae  occludentes varies. In epithelia in which anastomosing strands or fusion sites are sparse, such as certain kidney tubules, the intercellular pathway is partially permeable to water and solutes. In contrast, in epithelia in which the strands are numerous and extensively intertwined—for example, intestinal and urinary bladder epithelia—the intercellular region is highly impermeable.
However, in some epithelial cells, the number of strands does not directly correlate to the tightness of the seal. Differences in tightness between different zonulae occludentes could be explained by the presence of aqueous pores within individual zonula occludens strands (Fig. 5.17b). Recent experiments indicate that claudin-16 functions as an aqueous Mg2 channel between specific kidney epithelial cells. Similarly, claudin-2 is responsible for the presence of high-conductance aqueous pores in other kidney epithelia. Claudins not only form the backbone of the individual zonula occludens strand but also are responsible for the formation of extracellular aqueous channels. Thus, the combination and mixing ratios of claudins to occludins and other proteins found within individual paired zonula occludens strands determine tightness and selectivity of the seal between cells.
PDZ domains of associated intracellular attachment proteins
FIGURE 5.17 • Two transcellular and paracellular pathways for transport of substances across the epithelia. a. The transcellular pathway occurs across the plasma membrane of the epithelial cell and represents an active transport system that requires specialized energy-dependent membrane transport proteins and channels. The paracellular pathway occurs across the zonula occludens between two epithelial cells. The amount of water, electrolytes, and other small molecules transported through this pathway is contingent on the tightness of the zonula occludens. b. Structure of the extracellular and cytoplasmic portions of tight-junction strands. Two zonula occludens strands from neighboring cells fuse together in a zipperlike fashion and create a barrier to movement between the cells. Aqueous pores allow water to move between the cells. The permeability of the barrier depends on the mixture of claudins and occludins in the zipper seal. The cytoplasmic portion of the strand attracts PDZ-domain proteins that function in cell signaling.
The zonula occludens establishes functional domains in the plasma membrane.
As a junction, the zonula occludens controls not only the passage of substances across the epithelial layer but also the movement of lipid rafts containing specific proteins within the plasma membrane itself. The cell is able to segregate certain internal membrane proteins on the apical (free) surface and restrict others to the lateral or basal surfaces. In the intestine, for instance, the enzymes for terminal digestion of peptides and saccharides (dipeptidases and disaccharidases) are localized in the membrane of the microvilli of the apical surface. The NaK-ATPase that drives salt and transcellular water transport, as well as amino acid and sugar transport, is restricted to the lateral plasma membrane below the zonula occludens.
Anchoring junctions provide lateral adhesions between epithelial cells, using proteins that link into the cytoskeleton of adjacent cells. Two types of anchoring cell-to-cell junctions can be identified on the lateral cell surface:  zonula adherens (pl., zonulae adherentes), which inter acts with the network of actin filaments inside the cell; and  macula adherens (pl., maculae adherentes) or desmo some, which interacts with intermediate filaments