Talin force coupling underlies eukaryotic cell-substrate adhesion

Integrin-mediated cell adhesion and mechanotransduction are considered key innovations in animal evolution. Here, we show that these processes represent a specialization of an evolutionarily conserved force coupling mechanism that originated in unicellular organisms and is mediated by the actin-binding protein talin. In contrast to heterodimeric integrin receptors, talin is widely distributed in unicellular organisms, including amoebae. By comparing the molecular mechanics of talin-A from amoeboid cells with that of mammalian talin-1, we uncover a conserved role for talin in transmitting pN-scale forces, even in unicellular organisms lacking canonical integrin receptors but expressing the functional homologue SibA. Our data indicate that the critical evolutionary steps towards integrin-mediated cell adhesion in metazoan organisms were the specialization of talin as an adaptor protein allowing the activation of integrin receptors, the regulation of biochemical signaling by paxillin, FAK and YAP, and the control of cell adhesion turnover by KANK recruitment. Collectively, these experiments suggest a central but thus far underappreciated role for talin in the evolution of eukaryotic cell-substrate adhesion and force transmission.