Integrin activation by talin.

Abstract

The development and integrity of the cardiovascular system depends on integrins, a family of adhesion receptors, vitally important for homeostasis of animal species from fruit fly to man. Integrins are critical players in cell migration, cell adhesion, cell cycle progression, differentiation, and apoptosis. Consequently, integrins have a major impact on the patterning and functions of the blood and cardiovascular system. Integrins undergo conformational changes, which alter their affinity for ligands through a process operationally defined as integrin activation. Integrin activation is important for platelet aggregation, leukocyte extravasation, and cell adhesion and migration, thus influencing such processes as hemostasis, inflammation and angiogenesis. Recently, a series of studies have begun to define the mechanism of integrin activation by demonstrating that binding of a cytoskeletal protein, talin, to integrin beta subunit cytoplasmic tail is a last common step in integrin activation. These findings indicate that talin is likely to be at the center of converging signaling pathways regulating integrin activation.