We now complete our overview of cell–cell junctions and adhesion by briefly describing some of the more specialized adhesion mechanisms used in some tissues. In addition to those we have already discussed, at least three other super-families of cell–cell adhesion proteins are important: the integrins, the selectins, and the adhesive immunoglobulin (Ig) superfamily members. We shall discuss integrins in more detail later: their main function is in cell–matrix adhesion, but a few of them mediate cell–cell adhesion in specialized circumstances. Ca2+ dependence provides one simple way to distinguish among these classes of adhesion proteins experimentally. Selectins, like cadherins and integrins, require Ca2+ for their adhesive function; Ig superfamily members do not.
Selectins are cell-surface carbohydrate-binding proteins (lectins) that mediate a variety of transient cell–cell adhesion interactions in the bloodstream. Their main role, in vertebrates at least, is in governing the traffic of white blood cells into normal lymphoid organs and any inflamed tissues. White blood cells lead a nomadic life, roving between the bloodstream and the tissues, and this necessitates special adhesive behavior. The selectins control the binding of white blood cells to the endothelial cells lining blood vessels, thereby enabling the blood cells to migrate out of the bloodstream into a tissue.
Each selectin is a transmembrane protein with a conserved lectin domain that binds to a specific oligosaccharide on another cell (Figure 19–28A). There are at least three types: L-selectin on white blood cells, P-selectin on blood platelets and on endothelial cells that have been locally activated by an inflammatory response, and E-selectin on activated endothelial cells. In a lymphoid organ, such as a lymph (C) 0.1 µm node or the spleen, the endothelial cells express oligosaccharides that are recognized by L-selectin on lymphocytes, causing the lymphocytes to loiter and become trapped. At sites of inflammation, the roles are reversed: the endothelial cells switch on expression of selectins that recognize the oligosaccharides on white blood cells and platelets, flagging the cells down to help deal with the local emergency. Selectins do not act alone, however; they collaborate with integrins, which strengthen the binding of the blood cells to the endothelium. The cell–cell adhesions mediated by both selectins and integrins are heterophilic—that is, the binding is to a molecule of a different type: selectins bind to specific oligosaccharides on glycoproteins and glycolipids, while integrins bind to specific Ig-family proteins.
Selectins and integrins act in sequence to let white blood cells leave the bloodstream and enter tissues (Figure 19–28B). The selectins mediate a weak adhesion because the binding of the lectin domain of the selectin to its carbohydrate ligand is of low affinity. This allows the white blood cell to adhere weakly and reversibly to the endothelium, rolling along the surface of the blood vessel, propelled by the flow of blood. The rolling continues until the blood cell activates its integrins. As we discuss later, these transmembrane molecules can be switched into an adhesive conformation that enables them to latch onto specific macromolecules external to the cell—in the present case, proteins on the surfaces of the endothelial cells. Once it has attached in this way, the white blood cell escapes from the bloodstream into the tissue by crawling out of the blood vessel between adjacent endothelial cells.
Members of the Immunoglobulin Superfamily Mediate Ca2+-Independent Cell–Cell adhesion