Gene duplication and functional divergence during evolution of the cytoskeletal linker protein talin

The animal talins are large, modular proteins that link the actin cytoskeleton to the extracellular environment through interactions with beta-integrins and actin. Dictyostelium discoideum has two talins, Ta1A and Ta1B, which have distinct physiological roles in cell adhesion, cell differentiation, and cytokinesis. We previously identified a second talin gene in vertebrates. Thus, talin function in vertebrates is also due to the action Of multiple proteins. Using a phylogenomic approach we have determined that D. discoideum TalA/B and the animal talins are related by descent from a common ancestral talin and that duplication of TLN2 early in the chordate lineage produced TLN1. An additional duplication subsequently produced a second Talin-2 in teleost fishes and a second Talin-1 in Xenopus laevis. We also show that vertebrate Talin-2 mRNA is alternatively processed. In the invertebrate Drosophila melanogaster and in the non-vertebrate chordate Ciona intestinalis, which each have only one talin gene, alternative processing of talin mRNA also produces multiple talin species. Thus, in these organisms, talin function may be due to the action of more than one protein. To identify isoform-specific functions of vertebrate talins we have shown through proteomic analysis that mammalian Talin-1 and Talin-2 bind to different protein partners. Further characterization of the differences between animal talins, especially the direct comparison of talins in the model Urochordate C. intestinalis, which has one talin gene that produces two talins through alternative mRNA splicing, with Talin-1 and Talin-2 in model vertebrates, will provide an experimental system for Studying neofunctionalization or subfunctionalization of talin following the vertebrate talin gene duplication. (c) 2005 Elsevier B.V. All rights reserved.