Cell Surface Adhesion Receptors
 
 Cell surface adhesion receptors are molecules that mediate cell adhesion by binding to other molecules on the surface of an adjacent cell or to a component of the extracellular matrix. Many adhesion receptors have been described. Most of them belong to one of a small number of families of related molecules in which individual members share the same basic molecular structure. The principal families are the cadherins, the immunoglobulin (Ig) superfamily, the integrins, and the selectins (Fig. 1) as follows. 

Figure 1. Diagram showing the generalized molecular structures of the four principal families of cell-surface adhesion receptors. (From Ref. 7, with permission of BMJ Publishing Group.)
1. Cadherins
 In most tissues, a major contribution to intercellular adhesion is made by calcium-dependent cell adhesion molecules knows as cadherins (1). In general, these are simple transmembrane glycoproteins. The extracellular domain has an adhesion site toward the N-terminal region and several calcium-binding sites. Adhesive binding is mainly homophilic: a cadherin molecule on one cells binds to another cadherin molecule of the same type on the next cell. Linkage of the cytoplasmic domain to the cytoskeleton through proteins known as catenins is necessary for cadherin function. The best characterized is epithelial cadherin, E-cadherin. This appears very early in development, when it is involved in compaction of the eight-cell embryo and cell polarization. In adult epithelia—for example, intestinal epithelium—it is present on the lateral cell surfaces but is concentrated in intercellular junctions, known as the zonulae adherentes (see Cell Junctions; Intermediate Junction), which ring the apicolateral margins of cells. These junctions are characterized by a cortical ring of cytoskeleton, the major component of which is actin. Cadherins are also present in the nervous system, where they play an essential role in neural development.
The adhesive glycoproteins of the other major intercellular junctions of epithelia, the desmosomes are also members of the cadherin family (2). Their extracellular domains are very like those of cadherin, but their cytoplasmic domains differ, being specialized for forming desmosomal plaques and, thereby, attachment to the keratin intermediate filament cytoskeleton, rather than to actin.
2. Immunoglobulin Superfamily
 Another major group of cell-to-cell adhesion molecules are members of the Ig superfamily. Their extracellular portions are characterized by the presence of at least one, and usually multiple, immunoglobulin-like domains (3, 4). Included in this group are several nervous system cell adhesion molecules, such as the neural cell adhesion molecule (N-CAM), L-1, and TAG, which are involved in neuronal guidance and fasciculation. Several members of the immunoglobulin family are concerned with antigen recognition and adhesion in T cells. These include the following: the T-cell receptor (CD3) and its co-receptors CD4 and CD8, which together recognize the complexes of antigen peptide and major histocompatibility complexes on other cells; the major histocompatibility complex molecules themselves; and lymphocyte function related antigen 2 (LFA-2 or CD2), a receptor for another immunoglobulin-like molecule, LFA-3, expressed on other cells. Another group of immunoglobulin-like cell adhesion molecules includes the so-called intercellular adhesion molecules, ICAM-1, -2, and -3, which are more widely expressed, for example, on epithelial and endothelial cells, and V-CAM on endothelial cells. These are involved in the inflammatory response.
The immunoglobulin superfamily is large and diverse, probably because the basic structure of the immunoglobulin domain is versatile and readily adaptable to different binding functions. Among these molecules, however, the T cell receptor and the immunoglobulins themselves have somatically-variable domains necessary for antigen recognition. Members of the superfamily are even present in insects, where they are involved in nerve connections; the association of immunoglobulin-like domains in cellular recognition preceded the immune system in evolution.
3.   Integrins
 Both cell-to-cell and cell-to-matrix receptors are contained within this large family of adhesion molecules. Integrins are heterodimers consisting of one a chain and one b chain, both of which are necessary for adhesive binding (5). Seventeen different a chains and eight different b chains are now known. Integrins may be classified into subfamilies according to which b subunit is involved in the complex. Thus b1 integrin may associate with one of nine different a subunits, to give a series of matrix receptors of differing specificity. The b2 integrins, on the other hand, are a family of cell-to-cell adhesion molecules of lymphoid cells with three alternative a subunits. The classification is made more complicated because some a subunits can associate with different b subunits (for example, a6b1 and a6b4).
 Some integrins are apparently quite specific in their ligand-binding properties—for example, a5b1 for the Arg–Gly–Asp tripeptide sequence of fibronectin—whereas others are promiscuous—for example, avb3, once regarded as the vitronectin receptor, also binds fibronectin, fibrinogen, von Willebrand factor, thrombospondin, and ostepontin. An interesting example is a4b1, which binds both the IIICS domain of fibronectin and V-CAM on endothelial cells. To complicate matters further, individual cell types usually express multiple integrins. A good example to consider here is the blood platelets that express predominantly aIIbb3 (GPIIb/IIIa), which binds fibrinogen, fibronectin, von Willebrand factor, and vitronectin, but also lesser amounts of aVb3, a5b1, a2b1 (collagen), and a6b1 (laminin).
 4. Selectins
Most cellular interactions seem to entail homophilic or heterophilic protein–protein interactions. However, the selectins constitute a family of cell adhesion proteins that bind to carbohydrate. Selectins have lectin-like carbohydrate-binding domains at their extracellular N-terminal extremities (6) . One of these, L-selectin (L = leucocyte) is a “homing receptor,” mediating regionally specific adhesion of lymphocytes to endothelium in peripheral lymph nodes. This molecule is also involved in the adhesion of neutrophils to endothelium during the inflammatory response. Two other members of this family, E-selectin (E = endothelial) and P-selectin (P = platelet), also participate in the inflammatory response. E-selectin is unregulated on endothelial cells over a period of hours after stimulation by inflammatory mediators. P-selectin is contained within Wiebel–Palade bodies of endothelial cells and platelet a granules, from which it is rapidly mobilized on activation, mediating adhesion to neutrophils and monocytes.
 
References
1. M. Takeichi (1990) Cadherins: a molecular family important for selective cell–cell adhesion. Annu. Rev. Biochem. 59, 237–252. 
2. D. R. Garrod, M. A. J. Chidgey, and A. J. North (1996) Curr. Opin. Cell Biol. 8, 670–678. 
3. T. A. Springer (1990) Nature 346, 425–434. 
4. G. M. Edelman and K. L. Crossin (1991) Annu. Rev. Biochem. 60, 155–190. 
5. R. O. Hynes (1992). Cell 69, 11–25. 
6. M. P. Bevilaqua and R. M. Nelson (1993) J. Clin. Invest. 91, 379–387.
7. D. R. Garrod (1997). "Cell to cell and cell to matrix adhesion". In Basic Molecular and Cell Biology, 3rd ed., D. S. Latchman (ed.) BMJ Publishing Group, pp. 79–96.