The cytoplasmic domains are linked through a variety of intracellular proteins to components of the cell cytoskeleton. Through the cytoskeleton connection, CAMs are able to control and regulate diverse intracellular processes associated with cell adhesion, cell proliferation, and cell migration. In addition, CAMs are implicated in many other cellular functions such as intercellular and intracellular communications, cell recognition, regulation of intercellular diffusion barrier, generation of immune responses, and apoptosis. From early embryonic development, every type of tissue at every stage of differentiation is defined by the  expression of specific CAMs. Changes in the expression pattern of one or several CAMs may lead to pathologic changes during tissue differentiation or maturation. To date, about 50 CAMs have been identified, and they are classified on the bases of their molecular structure into four major families: cadherins, integrins, selectins, and the immunoglobin superfamily (see Fig. 5.18).
 Cadherins are represented by transmembrane Ca2dependent CAMs localized mainly within the zonula adherens. At these sites, cadherins maintain homotypic interactions with similar proteins from the neighboring cell. They are associated with a group of intracellular proteins (catenins) that link cadherin molecules to actin flaments of the cell cytoskeleton. Through this interaction, cadherins convey signals that regulate mechanisms of growth and cell differentiation. Cadherins control cell-tocell interactions and participate in cell recognition and embryonic cell migration. E-cadherin, the most studied member of this family, maintains the zonula adherens junction between  epithelial cells. It also acts as an important suppressor of epithelial tumor cells.
 Integrins are represented by two transmembrane glycoprotein subunits consisting of 15  and 9  chains. This composition allows for the formation of different combinations of integrin molecules that are able to interact with
FIGURE 5.18 • Cell adhesion molecules (CAMs). Cadherin and immunoglobin superfamily (IgSF) CAMs exhibit homotypic binding in which two identical molecules from the neighboring cells interact. Binding that occurs between different types of CAMs (e.g., selectins and integrins) is considered heterotypic binding (no identical pair of molecules reacts with each other).
various proteins (heterotypic interactions). Integrins interact with extracellular matrix molecules (such as collagens, laminin, and fibronectin) and with actin and intermediate flaments of the cell cytoskeleton. Through these interactions, integrins regulate cell adhesion, control cell movement and shape, and participate in cell growth and differentiation.
 Selectins are expressed on white blood cells (leukocytes) and endothelial cells and mediate neutrophil– endothelial cell recognition. This heterotypic binding initiates neutrophil migration through the endothelium of blood vessels into the extracellular matrix. Selectins are also involved in directing lymphocytes into accumulations of lymphatic tissue (homing procedure).