Cell Adhesion Molecules
Most cells are decorated with several types of proteins that allow their binding to other cells or to the extracellular matrix. The list of important functions of adhesion molecules is a long one, but one of their most fascinating and important roles is in choreographing tissue and organ formation during embryogenesis. If, for example, a chick embyro is dissociated into single cells and those cells mixed and placed together in a culture dish, there is a strong tendency for cells to reaggregate into clusters based on their tissue of origin. Such reaggregation is due to specific adhesion molecules that are not only expressed predominantly in certain organs but bind themselves.
As you would expect, all adhesion molecules are integral membrane proteins that have cytoplasmic, transmembrane and extracellular domains. The cytoplasmic tail often interacts with cytoskeletal proteins which serve as the actual anchor within the cell. The extracellular domains of adhesion molecules extend from the cell and bind to other cells or matrix by binding to other adhesion molecules of the same type (homophilic binding), binding to other adhesion molecules of a different type (heterophilic binding) or binding to an intermediary 'linker' which itself binds to other adhesion molecules.
Dozens of different adhesion molecules have been identified, but, at least so far, they fall into four major families:
- Cadherins cause adhesion via homophilic binding to other cadherins in a calcium-dependent manner (i.e. removal of extracellular calcium disrupts binding). Among other things, cadherins appear to be critical in segregating embryonic cells into tissues. As is the case for their role in desmosomes and adherens junctions, cadherins ultimately anchor cells through cytoplasmic actin and intermediate filaments.
- Immunoglobulin-like adhesion molecules include a large group of molecules that are generated from a smaller number of genes by alternative RNA splicing. Collectively, the function by both homophilic and heterophilic binding. The best-studied members of this group are the neural cell adhesion molecules (N-CAMs) which are expressed predominantly in nervous tissue and the intercellular cell adhesion molecules (ICAMs).
- Integrins are a diverse and large group of heterodimeric glycoproteins. The two subunits, designated as alpha and beta, both participate in binding. Integrins participate in cell-cell adhesion and are of great importance in binding and interactions of cells with components of the extracellular matrix such as fibronectin. Importantly, integrins facilitate "communication" between the cytoskeleton and extracellular matrix, allow each to influence the orientation and structure of the other. It is clear that interactions of integrins with the extracellular matrix can have profound effects on cell function, and events such as clustering of integrins activates a number of intracellular signally pathways. Another feature of integrins is that some exist in "active" and "inactive" states. For example, a group of integrins responsible for binding of white blood cells to endothelium are normally inactive, allowing the blood cells to circulate freely, but become activated in response to inflammatory mediators, resulting in the white cells being "pulled" from blood into inflammed tissues. It follows that deficits in expression of certain integrins can result in diseases characterized by abnormal inflammatory responses.
- Selectins are expressed primarily on leukocytes and endothelial cells and, like integrins, are important in many host defense mechanisms involving those cells. In contrast to other cell adhesion molecules, selectins bind to carbohydrate ligands on cells and the resulting binding forces are relatively weak. For example, selectin-mediated interactions between leukocytes and endothelial cells promotes rolling of the leukocytes along the endothelium and integrin-binding allows the leukocytes to be stopped in place.
Most cells express several members of the adhesion molecule families described above. Their importance in development, host defense and tissue organization and repair may be deduced and has, in several cases, been dramatically confirmed by study of spontaneous and targeted mutations of their encoding genes.
Back to the index of Junctions and Adhesion Molecules
References and Reviews
- Horwitz AF: Integrins and health. Scientific American 276:68, 1997.
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Last updated on June 01, 1997