 Immunoglobulin superfamily (IgSF). Many molecules involved in immune reactions share a common precursor element in their structure. However,  several other molecules with no known immunologic function also share this same repeat element. Together, the genes encoding these related molecules have been  defined as the immunoglobulin gene superfamily. It is one of the largest gene families in the human genome, and its glycoproteins perform a wide variety of important biologic functions. IgSF members mediate homotypic cell-to-cell adhesions and are represented by the intercellular cell adhesion molecule (ICAM), cell–cell adhesion mole cule (C-CAM), vascular cell adhesion molecule (VCAM), Down syndrome cell adhesion molecule (DSCAM), platelet endothelial cell adhesion molecules (PECAM), junctional adhesion molecules (JAM), and many others. These proteins play key roles in cell adhesion and differentiation, cancer and tumor metastasis, angiogenesis (new vessel formation),  inflammation, immune responses, and microbial  attachment, as well as many other functions.
The zonula adherens provides lateral adhesion between epithelial cells.
The integrity of epithelial surfaces depends in large part on the lateral adhesion of the cells with one another and their ability to resist separation. Although the zonula occludens involves a fusion of adjoining cell membranes, their resistance to mechanical stress is limited. Reinforcement of this region depends on a strong bonding site below the zonula occludens. Like the zonula occludens, this lateral adhesion device occurs in a continuous band or beltlike configuration around the cell; thus, the adhering junction is referred to as a zonula adherens. The zonula adherens is composed of the transmembrane cell adhesion molecule E-cadherin. On the cytoplasmic side, the tail of E-cadherin is bound to catenin (Fig. 5.19a). The resulting E-cadherin–catenin complex binds to vinculin and -actinin and is required for the interaction of cadherins with the actin filaments of the cytoskeleton. The extracellular components of the E-cadherin molecules from adjacent cells are linked by Ca2 ions or an additional extracellular link protein. Therefore, the morphologic and functional integrity of the zonula adherens is calcium dependent. Removal of Ca2 leads to dissociation of E-cadherin molecules and disruption of the junction. Recent studies indicate that the E-cadherin–catenin complex functions as a master molecule in regulating not only cell adhesion but also polarity, differentiation, migration, proliferation, and survival of epithelial cells.
When examined with the TEM, the zonula adherens is characterized by a uniform 15to 20-nm space between the opposing cell membranes (Fig. 5.19b). The intercellular space is of low electron density, appearing almost clear, but it is evidently occupied by extracellular components of adjacent E-cadherin molecules and Ca2 ions. Within the confines of the zonula adherens, a moderately electron-dense material called fuzzy plaque is found along the cytoplasmic side of the membrane of each cell. This material corresponds to the location of the cytoplasmic component of the Ecadherin–catenin complex and the associated proteins (-actinin and vinculin) into which actin filaments attach. Evidence also suggests that the fuzzy plaque represents the stainable substance in light microscopy, the terminal bar. Associated with the electron-dense material is an array of 6-nm actin flaments that stretch across the apical cytoplasm of the epithelial cell, the terminal web.