Complex Interactions at the Adherens Junction

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Science's STKE  06 Dec 2005:
Vol. 2005, Issue 313, pp. tw435
DOI: 10.1126/stke.3132005tw435

Two articles challenge the currently accepted model of interaction between the epithelial adherens junction and the actin cytoskeleton, in which α-catenin forms a stable link between β-catenin (which binds to the cytoplasmic tails of cadherins, junctional cell-cell adhesion proteins) and the actin cytoskeleton (binding to actin or to actin-associated proteins). Yamada et al. found that, in a pelleting assay, α-catenin pelleted with actin but did not promote pelleting with actin of an E-cadherin-β-catenin complex, whereas a chimeric protein in which α-catenin was covalently linked to β-catenin failed to bind actin. Thus, α-catenin bound to either actin or β-catenin but not to both simultaneously. Moreover, actin filaments failed to bind to E-cadherin-β-catenin-α-catenin complexes reconstituted on isolated patches of cadherin-containing epithelial cell membranes. Similarly, the actin-binding proteins α-actinin and vinculin failed to promote association between actin and the cadherin-catenin complex. Fluorescence recovery after photobleaching (FRAP) analysis of MDCK cells stably expressing green fluorescent protein-labeled proteins indicated that E-cadherin, β-catenin, and α-catenin showed similar mobility; in contrast, membrane-associated actin at cell-cell contacts was much more dynamic. Further, disruption of actin organization failed to affect mobility of the cadherin-catenin complex.

In the accompanying paper, Drees et al. found that cytoplasmic α-catenin was present as both a monomer and a homodimer. Consistent with the known overlap between the dimerization domain and the β-catenin binding domain, the authors found that the monomer bound more strongly to β-catenin. In contrast, α-catenin preferentially bound to actin as a homodimer. When actin filaments were incubated with cadherin-catenin complexes, some of the α-catenin dissociated from the complex and associated with actin; fluorescence loss in photobleaching (FLIP) analysis indicated that exchange of α-catenin associated with membrane proteins with that in a cytoplasmic pool occurred in living cells. The Arp2/3 complex nucleates actin filaments, a process that is regulated by Wiscott-Aldrich syndrome proteins (WASPs). α-catenin inhibited Arp2/3 binding to actin and suppressed the actin polymerization that occurred in the presence of Arp2/3 and the WASP activation domain, with the dimer suppressing polymerization more effectively. Thus, the authors conclude that the association between the cadherin-catenin complex and the actin cytoskeleton is likely dynamic. In their model, rather than linking the cadherin-β-catenin complex to the actin cytoskeleton, α-catenin--which exists in one form that is bound to β-catenin and another that can bind actin--may act as a molecular switch to regulate organization of the actin cytoskeleton. Gates and Peifer discuss the research in a minireview.

S. Yamada, S. Pokutta, F. Drees, W. I. Weis, W. J. Nelson, Deconstructing the cadherin-catenin-actin complex. Cell 123, 889-901 (2005). [PubMed]

F. Drees, S. Pokutta, S. Yamada, W. J. Nelson, W. I. Weis, α-Catenin is a molecular switch that binds E-cadherin-β-catenin and regulates actin-filament assembly. Cell 123, 903-915 (2005). [PubMed]

J. Gates, M. Peifer, Can 1000 reviews be wrong? Actin, α-catenin, and adherens junctions. Cell 123, 769-772 (2005). [PubMed]

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