Functional Modules

    α-catenin[Edit]

    α-catenin has broad activity that contributes to processes such as differentiation (i.e. commitment to a particular cell type), embryonic and tissue development, and cell migration (reviewed in [1, 2]). α-catenin is concentrated at cell-cell adhesion sites, e.g., tight junctions [3], and adherens junctions (reviewed in [4]), through its association with a related family member, beta (β)-catenin; this binding interaction is controlled by phosphorylation of either α- or β-catenin [5, 6] (reviewed in [7]) and phosphorylated β-catenin is expected to compete with homodimerziation of α-catenin [5, 8]. Dimerization of α-catenin creates a complex with functional domains at both ends that preferentially binds actin filaments, in contrast to the monomer which prefers E-cadherin-β-catenin complexes [9].

    Figure 1. Alpha (α)-catenin: This schematic diagram illustrates the molecular organization of α-catenin and provides examples for how α-catenin is represented in figures throughout this resource.
    Because β-catenin binds tightly to classical cadherins before they are transported to the cell surface [10, 11]), it was originally suggested that α-catenin formed an indirect link between adhesion receptors and the actin cytoskeleton via its association with β-catenin or other actin-binding proteins (e.g. vinculin and α-actinin) [11]. However, later work showed that α-catenin cannot bind the E-cadherin-β-catenin complex and actin simultaneously, nor does it bind actin indirectly through its binding partners, vinculin or α-actinin [12]. Thus, rather than serving as a bridge to the cytoskeleton, α-catenin appears to function primarily as a molecular switch that promotes stable cell-cell adhesions (e.g. adherens junctions). 

    Current models suggest that α-catenin promotes stronger adhesions in a few ways: 1) α-catenin may foster lateral clustering and activation of cadherins [13]; 2) α-catenin may recruit formins at nascent cell-cell contacts to produce new filaments that push against and bring the membranes together [14] (reviewed in [1, 2]); and 3) α-catenin may regulate membrane protrusive activity [15] and suppress Arp2/3 complex-mediated actin nucleation and polymerization at the leading edge in the lamellipodium [9] (reviewed in [2]).

    References

    1. Kobielak A., Fuchs E. Alpha-catenin: at the junction of intercellular adhesion and actin dynamics. Nat. Rev. Mol. Cell Biol. 2004; 5(8). [PMID: 15366705]
    2. Pokutta S., Drees F., Yamada S., Nelson WJ., Weis WI. Biochemical and structural analysis of alpha-catenin in cell-cell contacts. Biochem. Soc. Trans. 2008; 36(Pt 2). [PMID: 18363554]
    3. Watabe-Uchida M., Uchida N., Imamura Y., Nagafuchi A., Fujimoto K., Uemura T., Vermeulen S., van Roy F., Adamson ED., Takeichi M. alpha-Catenin-vinculin interaction functions to organize the apical junctional complex in epithelial cells. J. Cell Biol. 1998; 142(3). [PMID: 9700171]
    4. Takahashi N., Hiyama K., Kodaira M., Satoh C. The length polymorphism in the 5′ flanking region of the human beta-globin gene with denaturing gradient gel electrophoresis in a Japanese population. Hum. Genet. 1991; 87(2). [PMID: 2066111]
    5. Koslov ER., Maupin P., Pradhan D., Morrow JS., Rimm DL. Alpha-catenin can form asymmetric homodimeric complexes and/or heterodimeric complexes with beta-catenin. J. Biol. Chem. 1997; 272(43). [PMID: 9341178]
    6. Ozawa M., Kemler R. Altered cell adhesion activity by pervanadate due to the dissociation of alpha-catenin from the E-cadherin.catenin complex. J. Biol. Chem. 1998; 273(11). [PMID: 9497337]
    7.  Regulation of cell-cell adhesion by the cadherin-catenin complex. Biochem. Soc. Trans. 2008; 36(Pt 2). [PMID: 18363555]
    8. Pokutta S., Weis WI. Structure of the dimerization and beta-catenin-binding region of alpha-catenin. Mol. Cell 2000; 5(3). [PMID: 10882138]
    9. Drees F., Pokutta S., Yamada S., Nelson WJ., Weis WI. Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly. Cell 2005; 123(5). [PMID: 16325583]
    10. Aberle H., Butz S., Stappert J., Weissig H., Kemler R., Hoschuetzky H. Assembly of the cadherin-catenin complex in vitro with recombinant proteins. J. Cell. Sci. 1994; 107 ( Pt 12). [PMID: 7706414]
    11. Hinck L., Näthke IS., Papkoff J., Nelson WJ. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J. Cell Biol. 1994; 125(6). [PMID: 8207061]
    12. Yamada S., Pokutta S., Drees F., Weis WI., Nelson WJ. Deconstructing the cadherin-catenin-actin complex. Cell 2005; 123(5). [PMID: 16325582]
    13. Imamura Y., Itoh M., Maeno Y., Tsukita S., Nagafuchi A. Functional domains of alpha-catenin required for the strong state of cadherin-based cell adhesion. J. Cell Biol. 1999; 144(6). [PMID: 10087272]
    14. Kobielak A., Pasolli HA., Fuchs E. Mammalian formin-1 participates in adherens junctions and polymerization of linear actin cables. Nat. Cell Biol. 2004; 6(1). [PMID: 14647292]
    15. Abe K., Chisaka O., Van Roy F., Takeichi M. Stability of dendritic spines and synaptic contacts is controlled by alpha N-catenin. Nat. Neurosci. 2004; 7(4). [PMID: 15034585]
    Updated on: Wed, 26 Feb 2014 10:55:46 GMT
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