Talin force coupling underlies eukaryotic cell-substrate adhesion

Integrin-mediated cell adhesion and mechanotransduction are considered key innovations in animal evolution, enabling a specific and physically robust attachment of cells to the extracellular environment. Here, we show that this type of cell adhesion is a specification of an evolutionary conserved force coupling mechanism that originated in unicellular organisms and is mediated by the actin-binding protein talin. Unlike heterodimeric integrin receptors, talin is widely distributed in unicellular organisms, including amoebae. By comparing piconewton-scale mechanics of talin-A from amoeboid cells with that of mammalian talin-1, we uncover a conserved role of talin as a force transducer, transmitting mechanical forces of 6–8 pN into cells, even in unicellular organisms lacking integrin receptors. Our data show that the critical evolutionary steps towards integrin-mediated cell adhesion were the specification of talin as an adaptor protein allowing activation of integrin receptors, regulation of biochemical signalling via paxillin, FAK and YAP, and control of cell adhesion turnover by KANK recruitment. Collectively, our experiments identify a pivotal yet hitherto underappreciated role for talin in the evolution of eukaryotic cell-substrate adhesion and mechanotransduction.