Integrin-Mediated Cell-Matrix Interaction in Physiological and Pathological Blood Vessel Formation

Figure 1

Integrin activation. Integrins are a family of heterodimeric transmembrane adhesion receptors that bidirectionally relay signals with the extracellular matrix (ECM) and also with other cells. When activated, a conformational change increases the affinity, and clustering increases the avidity towards the ligand. (1) By inside-out signaling, integrins can reversibly undergo a conformational change from a bent inactive to an upright activated conformation with intermediate ligand affinity, at which the cytoplasmic domains are still close together. (2) Upon ligand binding, the integrin adopts a high-affinity conformation with a concomitant parting of the legs and a separation of the cytosolic α- and β-tails that unlocks docking sites for cytosolic molecules. (3) Clustering of ligand-occupied and activated integrins establishes a mechanical link between ECM and cytoskeleton and leads to the recruitment of scaffolding molecules and kinases. (4) The assembly of focal adhesions triggers intracellular signaling cascades. Details can be found in the text.