Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness.
Bottom Line: Kindlin appears to originate from a duplication of the sequence encoding the N-terminal fragment of talin (the talin head domain) with a subsequent insertion of the PH domain of separate origin.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: As anticipated, eGFP-K2 exhibited substantial colocalization with vinculin (colocalization coefficient R = 0.4). At the same time, the R values for eGFP-K3 or eGFP alone were eightfold lower (Figures 4, B–D, and 5A). Of interest, replacement of the N-terminal 241 or 441 amino acids of K3 with the corresponding sequences from K2 (1–265, construct 1; and 1– 461, construct 2; respectively) did not add to the extent of the vinculin colocalization of the resultant chimeras as compared with eGFPK3 or eGFP alone (Figures 4B and 5A). This result emphasized the importance of the remaining 261 C-terminal residues of K2 in the localization to focal adhesions. Indeed, when this C-terminal segment of K2 was fused to the N-terminal 441 amino acids of K3, the resultant chimeric protein (construct 6) gained the ability to colocalize with vinculin (R = 0.4; Figures 4C and 5A).
Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.