FIGURE 5.22 • Structure of a gap junction. a. Electron micrograph showing the plasma membranes of two adjoining cells forming a gap junction. The unit membranes (arrows) approach one another, narrowing the intercellular space to produce a 2-nm-wide gap. 76,000. b. Drawing of a gap junction showing the membranes of adjoining cells and the structural components of the membrane that form channels or passageways between the two cells. Each passageway is formed by a circular array of six subunits, dumbbell-shaped transmembrane proteins that span the plasma membrane of each cell. These complexes, called connexons, have a central opening of about 2-nm in diameter. The channels formed by the registration of the adjacent complementary pairs of connexons permit the flow of small molecules through the channel but not into the intercellular space. Conversely, substances in the intercellular space can permeate the area of a gap junction by flowing around the connexon complexes, but they cannot enter the channels. c. The diameter of the channel in an individual connexon is regulated by reversible changes in the conformation of the individual connexins.
Conformational changes in connexins leading to opening or closing gap junction channels have been observed with atomic force microscopy.
Earlier electron microscopy studies of isolated gap junctions suggested that the gap junction channels are opened and closed by twisting of the connexin subunits (Fig. 5.22c). Recent atomic force microscopy (AFM) studies provide a dynamic view of the conformational changes that take place in connexons. Channels in gap junctions can fluctuate rapidly between an open and a closed state through reversible changes in the conformation of individual connexins. The conformational change in connexin molecules that triggers closure of gap junction channels at their extracellular surface appears to be induced by Ca2 ions (Fig. 5.23). However, other calcium-independent gating mechanisms responsible for closing and opening of the cytoplasmic domains of gap junction channels have also been identified.
Mutations in connexin genes are major pathogenic factors in several diseases. For instance, a mutation in the gene encoding connexin-26 (Cx26) is associated with congenital deafness. The gap junctions formed by Cx26 are found in the inner ear and are responsible for recirculating K in the cochlear sensory epithelium. Other mutations affecting Cx46 and Cx50 genes have been identified in patients with inherited cataracts. Both proteins are localized within the lens of the eye and form extensive gap junctions between the epithelial cells and lens fibers. These gap junctions play a crucial role in delivering nutrients to and removing metabolites from the avascular environment of the lens.
A summary of the features of all of the junctions discussed in this chapter is found in Table 5.4.
Morphologic Specializations of the Lateral Cell Surface
Lateral cell surface folds (plicae) create interdigitating cytoplasmic processes of adjoining cells.
The lateral surfaces of certain epithelial cells show a tortuous boundary as a result of infoldings or plicae along the border of each cell with its neighbor (Fig. 5.24). These in-foldings increase the lateral surface area of the cell and are particularly prominent in epithelia that are engaged in fluid and electrolyte transport, such as the intestinal and