Integrins

Abstract

Integrins are cell adhesion receptors that are evolutionary old and that play important roles during developmental and pathological processes. The integrin family is composed of 24 alphabeta heterodimeric members that mediate the attachment of cells to the extracellular matrix (ECM) but that also take part in specialized cell-cell interactions. Only a subset of integrins (8 out of 24) recognizes the RGD sequence in the native ligands. In some ECM molecules, such as collagen and certain laminin isoforms, the RGD sequences are exposed upon denaturation or proteolytic cleavage, allowing cells to bind these ligands by using RGD-binding receptors. Proteolytic cleavage of ECM proteins might also generate fragments with novel biological activity such as endostatin, tumstatin, and endorepellin. Nine integrin chains contain an alphaI domain, including the collagen-binding integrins alpha1beta1, alpha2beta1, alpha10beta1, and alpha11beta1. The collagen-binding integrins recognize the triple-helical GFOGER sequence in the major collagens, but their ability to recognize these sequences in vivo is dependent on the fibrillar status and accessibility of the interactive domains in the fibrillar collagens. The current review summarizes some basic facts about the integrin family including a historical perspective, their structure, and their ligand-binding properties.

Fig. 1

Integrin founding fathers. Erkki Ruoslahti (left) and Richard O. Hynes (right) contributed seminal data in the early days of cell adhesion research leading to the characterization of the integrin family

Fig. 2

Representation of the integrin family. In vertebrates, the integrin family contains 24 heterodimers. Isolated species that have undergone genome duplication (e.g., Danio rerio) have more integrin family members. In higher vertebrates, the integrin family has 24 prototypical members

Fig. 3

Representation of a prototypical αI-domain-containing integrin heterodimer. Nine out of the 18 integrin α chains contains an αI domain, as shown, but all integrins contain a βI domain in the β subunit. a Representation of the domains in αI domain-containing integrin (stars divalent cation-binding sites. b Representation of arrangement of domains in αI-domain-containing integrin kying in a membrane