Herbert B Schiller and Reinhard Fässler
Max Planck Gesellschaft, Germany
Cell Biology

In vitro veritas? Using single integrin heterodimers embedded in phospholipid nanodiscs, Ye and colleagues substantiate that talin-head domain (THD) binding to the alpha(IIb)beta(3) tail enables the conformational switch associated with increased integrin affinity (activation) in the absence of receptor clustering or mechanical force. This is a fascinating step that will be important in resolving the ongoing debate surrounding integrin activation.

Ye and Ginsberg tackle a long-lasting controversy about the relative role of receptor clustering and ligand binding versus talin/kindlin tail binding in bringing the integrin to an active conformation. Several biophysical and biochemical experiments, using integrin-reconstituted liposomes and phospholipid nanodiscs together with cryo-electron microscopy, pinpoint THD binding to phospholipids and the beta(3) tail as key event in activation of beta(3) integrins. Nevertheless, a few questions still remain unanswered, including the low efficiency in THD-induced integrin unbending, why talin-1 and talin-2 double gene deletions in skeletal muscle permit integrin-extracellular matrix interaction {1}, why Talin overexpression in Kindlin-2-depleted Chinese hamster ovary cells fails to trigger integrin activation, why Kindlin loss is associated with impaired integrin activity etc.

References: {1} Conti et al. Development 2009, 136:3597-606 [PMID: 19793892].