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: From the functional perspective, mammalian K3 also stands apart from other kindlins. K1 and K2 function in cells constitutively adherent to extracellular matrix, where integrins serve as anchoring points for an assembly of focal adhesion complexes (Larjava et al., 2008; Malinin et al., 2010). Although all three kindlins are able to directly interact with integrins (Ma et al., 2008; Moser et al., 2008; Harburger et al., 2009), only K1 and K2 localize to and function as components of focal adhesions (Bialkowska et al., 2010). Although K3 can localize to podosomes, the specialized transient adhesion structures of hematopoietic cells (Ussar et al., 2006), it is not able to localize to focal adhesions, even when it is expressed in adherent cells (Bialkowska et al., 2010; Figure 4B). K3 distribution is also distinct from that of K2 in the context of the same cell, such as endothelial cells (Bialkowska et al., 2010).
Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.