Talin

Talin is a large cytoskeletal protein that anchors the actin cytoskeleton to the plasma membrane via integrin receptors, playing a central role in the formation and function of focal adhesions in adherent cells. In humans, two genes, TLN1 and TLN2, encode talin-1 and talin-2, respectively. These proteins are essential for cell adhesion, migration, and mechanotransduction, and they contribute to processes such as development, wound healing, and tissue remodeling. They also participate in platelet activation and thrombus formation.

Structure and isoforms: Talin is approximately 2,500 amino acids in length and consists of an N-terminal FERM (head) domain that binds β-integrin tails and phospholipids, followed by a large rod domain composed of multiple helical bundles with several vinculin-binding sites, and a C-terminal actin-binding site. Talin exists in an autoinhibited conformation, and mechanical force can unfold portions of the rod to expose sites for vinculin binding, strengthening the link between integrins and the actin cytoskeleton.

Activation and regulation: Talin is recruited to the plasma membrane and activated through signaling pathways that involve RIAM (an adaptor for Rap1) and PIP2. Activation promotes talin’s interaction with β-integrin tails, triggering integrin activation and the assembly of focal adhesions. The opened talin–actin–integrin complex transduces mechanical signals and coordinates adhesion dynamics.

Interactions and functions: Beyond integrins and actin, talin interacts with proteins such as vinculin, paxillin, and focal adhesion kinase (FAK). Through these interactions, talin participates in force transmission, focal-adhesion maturation, and downstream signaling that influences cell shape, migration, and tissue organization. Altered talin expression or function has been linked to cancer cell migration, metastasis, and other diseases.