Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness.
Bottom Line: Among the analyzed species, all metazoan lineages—but none of the premetazoans—had at least one kindlin-encoding gene, whereas talin was present in several premetazoan lineages.The presence of this segment enables K2 but not K3 to localize to focal adhesions.Thus emergence and subsequent functional specialization of kindlins allowed multicellular organisms to develop additional tissue-specific adaptations of cell adhesiveness.
Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.Show MeSH
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Mentions: Next we used the DIVERGE2 method to analyze functionally important residues in jawed vertebrate K3 (see Materials and Methods). This analysis identified 26 residues that were substantially functionally diverged from jawed vertebrate K1 and K2 clades (divergence value >1; Figure 6 and Supplemental Figure S12). Almost half of these functionally diverged residues (12 residues) are located in the C-end portion of the segment (117 residues from the F3 domain; Figure 6 and Supplemental Figure S12). The N-end and the middle of the K3 protein contain 14 functionally diverged residues in 586 residues of the alignment (Figure 6 and Supplemental Figure S12). The probability of observing 12 out of 26 residues within the small fragment of the alignment (∼17%) is extremely low (p = 0.00042 according to the binomial test). This result suggests that functional divergence of three vertebrate kindlin families is largely focused at the C-end of kindlin proteins.
Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.