Inside-out signaling through integrins.

Abstract

Rapid and yet precisely controlled changes in cell adhesion are a hallmark of a number of basic physiological processes. Many of these processes directly impact upon nephrology, including: (1) cell migration, which occurs during leukocyte infiltration into inflammatory sites (e.g., in glomerulonephritis, interstitial nephritis, and renal transplant rejection) and during embryogenesis (e.g., in development of the genitourinary system): and (2) platelet aggregation at sites of clot formation (e.g., in glomerulonephritis). The integrins are a family of adhesion molecules whose function is controlled by the cells that express them, and this properly makes them eminently suitable receptors for those situations that demand flexibility of the cellular adhesive phenotype. The control of integrin function occurs via regulatory signals that originate within the cell cytoplasm and are then transmitted to the external ligand-binding domain of the receptor. The generation and transmission of these "inside-out" signals are the subjects of intensive research that will be summarized in this review article.