Integrins are a family of adhesion proteins that interact with and sense neighbouring cells and the surrounding extracellular environment. They project from the surface of cells like antennae and transmit signals back and forth between the cell and its surroundings – this signalling controls a wide range of important cellular functions.

A network of cell adhesion proteins in the constellation of the proteome // Image by Adam Byron

A network of cell adhesion proteins in the constellation of the proteome

Amazingly, to signal, the integrin molecules change shape in the cell membrane, twisting from a compact “inactive” position to an extended “active” position. Depending on the shape of the integrins, different proteins attach to them to assist in the signalling process. But which proteins bind to different conformations of integrins, and how does this change the behaviour of a cell in response to its surroundings?

Several proteins, such as talin and kindlin, are known to play a part in activating integrins, and roles for proteins in integrin inactivation have also been described. To get a more complete picture of the protein landscape associated with integrins, we used proteomic techniques to try to analyse all the proteins linked to active and inactive integrins in cells. To fish out the integrins and their molecular colleagues from cells, we used monoclonal antibodies that only stuck to either the active or inactive shape of the integrin.

When we compared the associated protein landscapes of active and inactive integrins, we found that the protein composition was quite different. We detected activation-dependent proteins that we were expecting, like talin and kindlin. But we also identified a large number of proteins that had not been linked to integrin activation before.

In particular, we noticed that proteins linked to the microtubule cytoskeleton (see previous post) were enriched at active integrins. Using very cool microengineered surfaces patterned with monoclonal antibodies, we could see down the microscope that microtubules inside cells were indeed stabilised around areas of active integrins, but not areas of inactive integrins.

This shows that the behaviour of microtubules, which are important for the proper functioning of cells, can be regulated by the shape of integrins. We know that this shape can be modulated by proteins in the extracellular environment, which can activate integrins, so these results shed light on how cells can sense and respond to their surroundings.

This work was supported by the Wellcome Trust, the BBSRC, the American Heart Association and the University of Manchester.

Byron et al. A proteomic approach reveals integrin activation state-dependent control of microtubule cortical targeting. Nat. Commun. 6, 6135 (2015)