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Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness.

Meller J, Rogozin IB, Poliakov E, Meller N, Bedanov-Pack M, Plow EF, Qin J, Podrez EA, Byzova TV - Mol. Biol. Cell (2014)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.

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Functional divergence between K2 and K3. (A) Diagram showing K2, K3, and K2/K3 chimeric proteins used to identify areas responsible for localization of K2 to focal adhesions. Residue numbers at the fusion sites are indicated (number of the residue within K2 in black, corresponding number within K3 in blue). Bottom, domain structure of kindlins. F, FERMT domain; PH, pleckstrin homology domain; V, variable loop. (B–E) BAECs were transfected with GFP-K2, GFP-K3, or GFP-K2/3 chimeras and replated on fibronectin-coated coverslips (5 μg/ml) 24 h after the transfection. The cells were fixed 16 h later and stained for vinculin. Representative images were taken using fluorescence microscopy. Right, the corresponding schematic representations of the chimeras used. White arrows indicate focal adhesions. Scale bars, 5 μm.
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Figure 4: Functional divergence between K2 and K3. (A) Diagram showing K2, K3, and K2/K3 chimeric proteins used to identify areas responsible for localization of K2 to focal adhesions. Residue numbers at the fusion sites are indicated (number of the residue within K2 in black, corresponding number within K3 in blue). Bottom, domain structure of kindlins. F, FERMT domain; PH, pleckstrin homology domain; V, variable loop. (B–E) BAECs were transfected with GFP-K2, GFP-K3, or GFP-K2/3 chimeras and replated on fibronectin-coated coverslips (5 μg/ml) 24 h after the transfection. The cells were fixed 16 h later and stained for vinculin. Representative images were taken using fluorescence microscopy. Right, the corresponding schematic representations of the chimeras used. White arrows indicate focal adhesions. Scale bars, 5 μm.

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).


Emergence and subsequent functional specialization of kindlins during evolution of cell adhesiveness.

Meller J, Rogozin IB, Poliakov E, Meller N, Bedanov-Pack M, Plow EF, Qin J, Podrez EA, Byzova TV - Mol. Biol. Cell (2014)

Functional divergence between K2 and K3. (A) Diagram showing K2, K3, and K2/K3 chimeric proteins used to identify areas responsible for localization of K2 to focal adhesions. Residue numbers at the fusion sites are indicated (number of the residue within K2 in black, corresponding number within K3 in blue). Bottom, domain structure of kindlins. F, FERMT domain; PH, pleckstrin homology domain; V, variable loop. (B–E) BAECs were transfected with GFP-K2, GFP-K3, or GFP-K2/3 chimeras and replated on fibronectin-coated coverslips (5 μg/ml) 24 h after the transfection. The cells were fixed 16 h later and stained for vinculin. Representative images were taken using fluorescence microscopy. Right, the corresponding schematic representations of the chimeras used. White arrows indicate focal adhesions. Scale bars, 5 μm.
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Related In: Results  -  Collection

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Figure 4: Functional divergence between K2 and K3. (A) Diagram showing K2, K3, and K2/K3 chimeric proteins used to identify areas responsible for localization of K2 to focal adhesions. Residue numbers at the fusion sites are indicated (number of the residue within K2 in black, corresponding number within K3 in blue). Bottom, domain structure of kindlins. F, FERMT domain; PH, pleckstrin homology domain; V, variable loop. (B–E) BAECs were transfected with GFP-K2, GFP-K3, or GFP-K2/3 chimeras and replated on fibronectin-coated coverslips (5 μg/ml) 24 h after the transfection. The cells were fixed 16 h later and stained for vinculin. Representative images were taken using fluorescence microscopy. Right, the corresponding schematic representations of the chimeras used. White arrows indicate focal adhesions. Scale bars, 5 μm.
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Cardiology, Joseph J. Jacobs Center for Thrombosis and Vascular Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195.

Show MeSH
Related in: MedlinePlus