Anti-TLN2 monoclonal antibody, clone FQS3647(3)

Talin interacts with beta-integrin tails and actin to control integrin activation, thus regulating focal adhesion dynamics and cell migration. There are two talin genes, Tln1 and Tln2, which encode talin1 and talin2, and it is generally believed that talin2 functions redundantly with talin1. However, we show here that talin2 has a higher affinity to beta 1-integrin tails than talin1. Mutation of talin2 S339 to leucine, which can cause Fifth Finger Camptodactyly, a human genetic disease, completely disrupted its binding to beta-integrin tails. Also, substitution of talin1 C336 with Ser enhanced the affinity of talin1, whereas substitution of talin2 S339 with Cys diminished that of talin2. Further computational modeling analysis shows that talin2 S339 formed a hydrogen bond with E353, which is critical for inducing key hydrogen bonds between talin2 N326 and beta 1-integrin R760, and between talin2 K327 and beta 1-integrin D759. Mutation at any of these residues significantly diminished the interaction of talin2 with beta 1-integrin tails. These hydrogen bonds were not observed in talin1/beta 1-integrin, but did exist in talin1C336S/beta 1-integrin complex. These results suggest that talin2 S339 forms a hydrogen bond with E353 to mediate its high affinity to beta 1-integrin.

There are two vertebrate talin genes, TLN1 and TLN2, which encode talin1 and talin2. Talin1 governs integrin activation, thus regulating focal adhesion (FA) assembly, cell migration and invasion, but the biological function of talin2 remains to be elucidated and not too long ago talin2 was presumed to function redundantly with talin1. Recent studies have shown distinct differences between talin2 and talin1. The promoter of TLN2 is different from that of TLN1 in their size and binding to different transcription factors. Talin2 has a higher affinity to beta-integrins than talin1. Talin2 regulates traction force generation, focal adhesion dynamics and invadopodium formation, thus controlling tumor cell migration, invasion and metastasis. Also, talin2 is enriched in the myotendinous junction (MTJ) in striated muscle, costameres and intercalated disks (ICDs) of cardiac myofibrils, and atherosclerotic plaques of blood vessels, thus regulating cardiovascular integrity. In this review, we discuss the differences between talin1 and talin2, in genome, protein expression pattern, affinity with integrins, traction force generation, and provide a glance at the roles of talin2 in cancer cell invasion and cardiovascular function.