Talin (also called filopodin) plays an important role in initiating actin filament growth in motile cell protrusions. It is responsible for linking the cytoplasmic domains of integrins to the actin-based cytoskeleton, and is involved in vinculin, integrin and actin interactions. At the leading edge of motile cells, talin colocalises with the hyaluronan receptor layilin in transient adhesions, some of which become more stable focal adhesions (FA). During this maturation process, layilin is replaced with integrins, where localized production of PI(4,5)P(2) by type 1 phosphatidyl inositol phosphate kinase type 1gamma (PIPK1gamma) is thought to play a role in FA assembly. Talins are composed of a N-terminal region FERM domain which us made up of 3 subdomains (N, alpha-, and C-lobe; or- A-lobe, B-lobe, and C-lobe; or F1, F2, and F3) connected by short linkers, a talin rod which binds vinculin, and a conserved C-terminal region with actin- and integrin-binding sites. There are 2 additional actin-binding domains, one in the talin rod and the other in the FERM domain. Both the F2 and F3 FERM subdomains contribute to F-actin binding. Subdomain F3 of the FERM domain contains overlapping binding sites for integrin cytoplasmic domains and for the type 1 gamma isoform of PIP-kinase (phosphatidylinositol 4-phosphate 5-kinase). The FERM domain has a cloverleaf tripart structure . F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.
Jiyao W et al.(2023). "The conserved domain database in 2023.",