The interaction of talin with the cell membrane is essential for integrin activation and focal adhesion formation

Significance Vertebrate cell growth, division, locomotion, morphogenesis, and development rely on the dynamic interactions of cells with extracellular matrix components via cell surface complexes termed focal adhesions that are composed of heterodimeric αβ integrin receptors, associated signaling molecules, and the large cytoskeletal protein talin. While it is known that talin activation and binding to β-integrin requires interactions with lipids, little is known regarding the structure and function of inactive vs. activated talin, and what is known is often disputed. Here we report that talin binding to the cell membrane seems necessary for integrin activation and focal adhesion formation, a finding that significantly advances our understanding of integrin activation and might aid the development of novel integrin therapeutic agents.