The mechanical signals within the extracellular matrix (ECM) regulate cell growth, proliferation and differentiation, and integrins function as the hub between the ECM and cellular actin. Focal adhesions (FAs) are multi‑protein, integrin‑containing complexes, acting as tension‑sensing anchoring points that bond cells to the extracellular microenvironment. Talin‑1 serves as the central protein of FAs that participates in the activation of integrins and connects them with the actin cytoskeleton. As a cytoplasmic protein, Talin‑1 consists of a globular head domain and a long rod comprised of a series of α‑helical bundles. The unique structure of the Talin‑1 rod domain permits folding and unfolding in response to the mechanical stress, revealing various binding sites. Thus, conformation changes of the Talin‑1 rod domain enable the cell to convert mechanical signals into chemical through multiple signaling pathways. The present review discusses the binding partners of Talin‑1, their interactions, effects on the cellular processes, and their possible roles in diseases.

Integrins are heterodimeric membrane-spanning adhesion receptors that are essential for a wide range of biological functions. Control of integrin conformational states is required for bidirectional signalling across the membrane. Key components of this control mechanism are the transmembrane and cytoplasmic domains of the alpha and beta subunits. These domains are believed to interact, holding the integrin in the inactive state, while inside-out integrin activation is accompanied by domain separation. Although there are strong indications for domain interactions, the majority of evidence is insufficient to precisely define the interaction interface. The current best model of the complex, derived from computational calculations with experimental restraints, suggests that integrin activation by the cytoplasmic protein talin is accomplished by steric disruption of the alpha/beta interface. Better atomic-level resolution structures of the alpha/beta transmembrane/cytoplasmic domain complex are still required for the resting state integrin to corroborate this. Integrin activation is also controlled by competitive interactions involving the cytoplasmic domains, particularly the beta-tails. The concept of the beta integrin tail as a focal adhesion interaction \'hub\' for interactions and regulation is discussed. Current efforts to define the structure and affinity of the various complexes formed by integrin tails, and how these interactions are controlled, e.g. by phosphorylation and localization, are described.