Figure 19–22 Scaffold proteins at the tight junction. the scaffold proteins ZO-1, ZO-2, and ZO-3 are concentrated beneath the plasma membrane at tight junctions. Each of the proteins contains multiple protein-binding domains, including three pDZ domains, an Sh3 domain, and a GK domain, linked together like beads on a flexible string. these domains enable the proteins to interact with each other and with numerous other partners, as indicated here, to generate a tightly woven protein network that organizes the sealing strands of the tight junction and links them to the actin cytoskeleton. Scaffold proteins with similar structure help organize other junctional complexes, including those at neural synapses.
cytoplasm of one to that of the other. These channels are called gap junctions.
Gap junctions are present in most animal tissues, including connective tissues as well as epithelia and heart muscle. Each gap junction appears in conventional electron micrographs as a patch where the membranes of two adjacent cells are separated by a uniform narrow gap of about 2–4 nm (Figure 19–23). The gap is spanned by channel-forming proteins, of which there are two distinct families, called the connexins and the innexins. Connexins are the predominant gap-junction proteins in vertebrates, with 21 isoforms in humans. Innexins are found in the gap junctions of invertebrates.
Gap junctions have a pore size of about 1.4 nm, which allows the exchange of inorganic ions and other small water-soluble molecules, but not of macromolecules such as proteins or nucleic acids (Figure 19–24). An electric current injected into one cell through a microelectrode causes an electrical disturbance in the neighboring cell, due to the flow of ions carrying electric charge through gap junctions. This electrical coupling via gap junctions serves an obvious purpose in tissues containing electrically excitable cells: action potentials can spread rapidly from cell to cell, without the delay that occurs at chemical synapses. In vertebrates, for example, electrical coupling through gap junctions synchronizes the contractions of heart muscle cells as well as those of the smooth muscle cells responsible for the peristaltic movements of the intestine. Gap junctions also occur in many tissues whose cells are not electrically excitable. In principle, the sharing of small metabolites and ions provides a mechanism for coordinating the activities of individual cells in such tissues and for smoothing out random fluctuations in small-molecule concentrations in different cells.
a Gap-Junction Connexon Is Made of Six transmembrane Connexin Subunits
Connexins are four-pass transmembrane proteins, six of which assemble to form a hemichannel, or connexon. When the connexons in the plasma membranes of two cells in contact are aligned, they form a continuous aqueous channel that connects the two cell interiors (Figure 19–25). A gap junction consists of many such connexon pairs in parallel, forming a sort of molecular sieve. Not only does this sieve provide a communication channel between cells, but it also provides a form of cell–cell adhesion that supplements the cadherinand claudin-mediated adhesions we discussed earlier.
Figure 19–23 Gap junctions as seen in the electron microscope. (a) thin-section and (B) freeze-fracture electron micrographs of a large and a small gap-junction plaque between fibroblasts in culture. In (B), each gap junction is seen as a cluster of homogeneous intramembrane particles. Each intramembrane particle corresponds to a connexon (see Figure 19–25). (From N.B. Gilula, in Cell Communication [r.p. Cox, ed.],  pp. 1–29. New York: Wiley, 1974.)
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