There are some exceptions to these rules. Some integrins, for example, mediate cell–cell rather than cell–matrix attachment. Moreover, there are other types of cell adhesion molecules that can provide transient cell–cell attachments more flimsy than anchoring junctions, but sufficient to stick cells together in special circumstances.
We begin the chapter with a discussion of the major forms of cell–cell junctions. We then consider in turn the extracellular matrix of animals, the structure and function of integrin-mediated cell–matrix junctions, and, finally, the plant cell wall, a special form of extracellular matrix.
Cell–cell junctions come in many forms and can be regulated by a variety of mechanisms. The best understood and most common are the two types of cell– cell anchoring junctions, which employ cadherins to link the cytoskeleton of one cell with that of its neighbor. Their primary function is to resist the external forces that pull cells apart. The epithelial cells of your skin, for example, must remain tightly linked when they are stretched, pinched, or poked. Cell–cell anchoring junctions must also be dynamic and adaptable, so that they can be altered or rearranged when tissues are remodeled or repaired, or when there are changes in the forces acting on them.
In this section, we focus primarily on the cadherin-based anchoring junctions. We then briefly describe tight junctions and gap junctions. Finally, we consider the more transient cell–cell adhesion mechanisms employed by some cells in the bloodstream.
Cadherins Form a Diverse Family of adhesion Molecules
Cadherins are present in all multicellular animals whose genomes have been analyzed. They are also present in the choanoflagellates, which can exist either as free-living unicellular organisms or as multicellular colonies and are thought to be representatives of the group of protists from which all animals evolved. Other eukaryotes, including fungi and plants, lack cadherins, and they are also absent from bacteria and archaea. Cadherins therefore seem to be part of the essence of what it is to be an animal.
The cadherins take their name from their dependence on Ca2+ ions: removing Ca2+ from the extracellular medium causes adhesions mediated by cadherins to come apart. The first three cadherins to be discovered were named according to the main tissues in which they were found: E-cadherin is present on many types of epithelial cells; N-cadherin on nerve, muscle, and lens cells; and P-cadherin on cells in the placenta and epidermis. All are also found in other tissues. These and other classical cadherins are closely related in sequence throughout their extracellular and intracellular domains.
There are also a large number of nonclassical cadherins that are more distantly related in sequence, with more than 50 expressed in the brain alone. The nonclassical cadherins include proteins with known adhesive function, such as the diverse protocadherins found in the brain, and the desmocollins and desmogleins that form desmosomes (see Table 19–1). Other family members are involved primarily in signaling. Together, the classical and nonclassical cadherin proteins constitute the cadherin superfamily (Figure 19–4), with more than 180 members in humans.
Anchoring junctions between cells are usually symmetrical: if the linkage is to actin in the cell on one side of the junction, it will be to actin in the cell on the other side. In fact, the binding between cadherins is generally homophilic (liketo-like, Figure 19–5): cadherin molecules of a specific subtype on one cell bind to cadherin molecules of the same or closely related subtype on adjacent cells.