Activation of Integrins

For a cell to migrate through the ECM, the cell's attachment to the ECM must be made and broken quickly.

This is facilitated by membrane-bound integrins rapidly transitioning between an active state, which forms attachments, and an inactive state that does not.

In the inactive conformation, the tails of the integrin dimer are compactly locked together, preventing integrin from binding ECM proteins or cytoskeletal filaments.

Integrins can be activated from outside the cell in the “outside-in” mechanism or internally in the "inside-out" mechanism.

In the "outside-in" mechanism, ECM proteins like fibronectin bind to integrin's extracellular domain. The tails unhook, and integrin switches from an inactive state to an active state, exposing the binding sites for cytosolic adaptor proteins.

Conversely, in the "inside-out" mechanism, adaptor proteins like talin bind integrin's cytosolic beta chain, thus breaking the alpha-beta link and forcing apart the integrin legs. The active integrin can now bind ECM proteins.