Integrins are receptors that mediate attachment between a cell and the tissues surrounding it, which may be other cells or the extracellular matrix (ECM). They also play a role in cell signaling and thereby define cellular shape, mobility, and regulate the cell cycle.

Typically, receptors inform a cell of the molecules in its environment and the cell evokes a response. Not only do integrins perform this outside-in signalling, but they also operate an inside-out mode. Thus, they transduce information from the ECM to the cell as well as reveal the status of the cell to the outside, allowing rapid and flexible responses to changes in the environment, for example to allow blood coagulation by platelets.

There are many types of integrin, and many cells have multiple types on their surface. Integrins are of vital importance to all animals and have been found in all animals investigated, from sponges to mammals. Integrins have been extensively studied in humans.

Integrins work alongside other proteins such as cadherins, cell adhesion molecules and selectins to mediate cell-cell and cell-matrix interaction and communication.

Structure

Integrins are obligate heterodimers containing two distinct chains, called the α (alpha) and β (beta) subunits. In mammals, 19 α and 8 β subunits have been characterized, whereas the Drosophila genome encodes only five α and two β subunits, and the Caenorhabditis nematodes possess two α and one β genes. Both the α and β subunits contain two separate tails, both of which penetrate the plasma membrane and possess small cytoplasmic domains.

alpha

beta

In addition, variants of some of the subunits are formed by differential splicing, for example 4 variants of the beta-1 subunit exist. Through different combinations of these alpha and beta subunits, some 24 unique integrins are generated, although the number varies according to different studies.

Integrin subunits span the plasma membrane and in general have very short cytoplasmic domains of about 40-70 amino acids. The exception is the beta-4 subunit which has a cytoplasmic domain of 1088 amino acids, one of the largest known cytoplasmic domains of any membrane protein. Outside the cell plasma membrane, the alpha and beta chains lie close together along a length of about 23 nm, the final 5 nm N-termini of each chain form a ligand-binding region for the ECM, or extracellular matrix.

The molecular mass of the integrin subunits can vary from 90 kDa to 160 kDa. β subunits have four cysteine-rich repeated sequences. Both α and β subunits bind several divalent cations. The role of the α subunit is unknown, but they may stabilize the folds of the protein. The β subunits are more interesting: they are directly involved in coordinating at least some of the ligands that integrins bind.