The epithelium of the small intestine provides a good illustration of tight-junction structure and function (see Figure 19–2). This epithelium has a simple columnar structure; that is, it consists of a single layer of tall (columnar) cells. These are of several differentiated types, but the majority are absorptive cells, specialized for uptake of nutrients from the internal cavity, or lumen, of the gut. The absorptive cells have to transport selected nutrients across the epithelium from the lumen into the extracellular fluid on the other side. From there, these nutrients diffuse into small blood vessels to provide nourishment to the organism. This transcellular transport depends on two sets of transport proteins in the plasma membrane of the absorptive cell. One set is confined to the apical surface of the cell (facing the lumen) and actively transports selected molecules into the cell from the gut. The other set is confined to the basolateral (basal and lateral) surfaces of the cell, and it allows the same molecules to leave the cell by passive transport into the extracellular fluid on the other side of the epithelium. For this transport activity to be effective, the spaces between the epithelial cells must be tightly sealed, so that the transported molecules cannot leak back into the gut lumen through these spaces (Figure 19–18). Moreover, the transport proteins must be correctly distributed in the plasma membranes: the apical transporters must be delivered to the cell apex and must not be allowed to drift to the basolateral membrane, and the basolateral transporters must be delivered to and remain in the basolateral membrane. Tight junctions, besides sealing the gaps between the cells, also function as “fences” that help prevent apical or basolateral proteins from diffusing into the wrong region.
The sealing function of tight junctions is easy to demonstrate experimentally: a low-molecular-weight tracer added to one side of an epithelium will generally not pass beyond the tight junction (Figure 19–19). This seal is not absolute, however. Although all tight junctions are impermeable to macromolecules, their permeability to ions and other small molecules varies. Tight junctions in the epithelium lining the small intestine, for example, are 10,000 times more permeable to inorganic ions, such as Na+, than the tight junctions in the epithelium lining the urinary bladder. The movement of ions and other molecules between epithelial cells is called paracellular transport, and tissue-specific differences in transport rates generally result from differences in the proteins that form tight junctions.
tight Junctions Contain Strands of transmembrane adhesion proteins
When tight junctions are visualized by freeze-fracture electron microscopy, they are seen as a branching network of sealing strands that completely encircles the
Figure 19–17 Desmosomes, hemidesmosomes, and the intermediate filament network. the keratin intermediate filament networks of adjacent cells—in this example, epithelial cells of the small intestine—are indirectly connected to one another through desmosomes, and to the basal lamina through hemidesmosomes.
plasma membranes of adjacent cells apical end of each cell in the epithelial sheet (Figure 19–20A and B). In conventional electron micrographs, the outer leaflets of the two interacting plasma membranes are tightly apposed where sealing strands are present (Figure 19–20C). Each sealing strand is composed of a long row of transmembrane homophilic adhesion proteins embedded in each of the two interacting plasma membranes. The extracellular domains of these proteins adhere directly to one another to occlude the intercellular space (Figure 19–21).