Integrin activation: All we need is talin

Integrins regulate cell migration and cell-matrix adhesion, which are important processes for development and disease. Genetic studies investigating mechanisms involved in integrin activation indicated that both talin and kindlins are involved by binding the integrin beta subunit cytoplasmic domain. Nevertheless, it is uncertain whether these molecules are sufficient for integrin activation. By developing a purified system to recreate the final events in integrin activation, Mark Ginsberg, Kenneth Taylor and colleagues now report in the Journal of Cell Biology that talin binding to the beta3 tail is sufficient for activation of integrin alphaIIb beta3. The authors incorporated alphaIIb beta3 into liposomes and used cryo-electron tomography to establish the incorporation of the integrin and its orientation. When talin head domain was present, the integrin was activated showing that talin is sufficient for integrin activation. Supporting this, talin also activated a beta3 mutant that is impaired for kindlin binding. The authors went on to demonstrate that for activation by talin, the integrin is required to be embedded in a phospholipid bilayer, and the talin is required to bind the phospholipid. Lastly, quantitative electron microscopy analysis of phospholipid nanodiscs with single integrins embedded in them revealed that talin activates un-clustered integrins, changing their conformation to an extended form. This study resolves the uncertainty as to whether talin is sufficient to activate and extend un-clustered integrins, and paves the way for understanding the physiological events involved in inside-out integrin signalling.

• Ye F, Hu G, Taylor D, Ratnikov B, Bobkov AA, McLean MA, Sligar SG, Taylor KA, Ginsberg MH. Recreation of the Terminal Events in Physiological Integrin Activation. J Cell Biol. 2010 Jan 4 [Epub ahead of print]. PubMed