Integrins and Extracellular Matrix

Integrin molecular weights using SDS-PAGE.

The 22 different integrin combinations in mammals may recognize different or overlapping ECM proteins.

Cell adhesion mediates cell communication and regulates tissue development and maintenance. Cell-ECM adhesion influences disease states through processes such as angiogenesis, apoptosis, and inflammation and is also critical for cell signal transduction. Knowledge of the molecular mechanisms involved in these interactions will facilitate the development of novel therapeutics for diseases such as arthritis and cancer.

Integrins are a class of cell surface proteins that anchor cells to ECM proteins and to endothelial surfaces, triggering signaling events that regulate cell survival, proliferation, and migration. Functional integrins are heterodimeric, containing one α and one β transmembrane glycoprotein subunit. The resulting 22 different integrin combinations in mammals (shown at right) may recognize different or overlapping ECM proteins. Certain integrins can also bind to soluble ligands or to counter-receptors on adjacent cells, such as the intracellular adhesion molecules (ICAMs), resulting in aggregation of cells.

Integrins bind using a population approach. Each integrin binds its ligand with relatively low affinity. Larger local concentrations of integrins yield proportionately stronger adhesions (called focal contacts), thus allowing many different areas on the cell membrane to have independent control over local binding or detachment. Integrin binding also induces extracellular signaling. Merck is a leader in antibodies, proteins and assays for the identification, localization and blocking of cellular adhesion mechanisms.