[4] The presence of integrins allows rapid and flexible responses to events at the cell surface (e.g. signal platelets to initiate an interaction with coagulation factors).

[3] Integrins work alongside other proteins such as cadherins, the immunoglobulin superfamily cell adhesion molecules, selectins and syndecans, to mediate cell–cell and cell–matrix interaction.

Several genes code for multiple isoforms of these subunits, which gives rise to an array of unique integrins with varied activity.

[6] The α and β subunits are both class I transmembrane proteins, so each penetrates the plasma membrane once, and can possess several cytoplasmic domains.

Through different combinations of the α and β subunits, 24 unique mammalian integrins are generated, excluding splice- and glycosylation variants.

The X-ray crystal structure obtained for the complete extracellular region of one integrin, αvβ3,[1] shows the molecule to be folded into an inverted V-shape that potentially brings the ligand-binding sites close to the cell membrane.

Perhaps more importantly, the crystal structure was also obtained for the same integrin bound to a small ligand containing the RGD-sequence, the drug cilengitide.

The interaction of such sequences with integrins is believed to be a primary switch by which ECM exerts its effects on cell behaviour.

It appears that the integrin transmembrane helices are tilted (see "Activation" below), which hints that the extracellular chains may also not be orthogonal with respect to the membrane surface.

As the "footprint" that an antibody makes on its binding target is roughly a circle about 3 nm in diameter, the resolution of this technique is low.

Nevertheless, these so-called LIBS (Ligand-Induced-Binding-Sites) antibodies unequivocally show that dramatic changes in integrin shape routinely occur.

When released into the cell membrane, newly synthesized integrin dimers are speculated to be found in the same "bent" conformation revealed by the structural studies described above.

In cells, the priming is accomplished by a protein talin, which binds to the β tail of the integrin dimer and changes its conformation.

Unfortunately, the helices are too long, and recent studies suggest that, for integrin gpIIbIIIa, they are tilted with respect both to one another and to the plane of the membrane.

Talin binding alters the angle of tilt of the β3 chain transmembrane helix in model systems and this may reflect a stage in the process of inside-out signalling which primes integrins.

Together with signals arising from receptors for soluble growth factors like VEGF, EGF, and many others, they enforce a cellular decision on what biological action to take, be it attachment, movement, death, or differentiation.

The integrins thus serve to link two networks across the plasma membrane: the extracellular ECM and the intracellular actin filamentous system.

The clusters likely provide sufficient intracellular binding sites to permit the formation of stable signaling complexes on the cytoplasmic side of the cell membrane.

Integrins can regulate the receptor tyrosine kinase signaling by recruiting specific adaptors to the plasma membrane.

The tissue stiffness and matrix composition can initiate specific signaling pathways regulating cell behavior.

Clustering and activation of the integrins/actin complexes strengthen the focal adhesion interaction and initiate the framework for cell signaling through assembly of adhesomes.

[27] Integrins are present at the growth cone of damaged PNS neurons and attach to ligands in the ECM to promote axon regeneration.