Cadherins trade bonds

Cadherins trade bonds C adherins are transmembrane, calcium-dependent adhesion molecules that assemble into ad-herens junctions to connect neighboring cells. Hong et al. reveal how cadherins regulate junction dynamics by changing their adhesive bonds (1). Adherens junctions must rapidly assemble and disassemble to accommodate continuous cell movements within tissues (2). This creates a fundamental problem for cadherins, says Sergey Troyanovsky, from Northwestern University in Chicago, IL. " To quickly assemble a fi rm junction, the cadherin bonds must be very strong, " Troy-anovsky explains. " But then how can they disassemble so rapidly as well? " Studying this question is complicated by the fact that cadherin-mediated adhesion depends not only on the adhesion molecule's extracellular domain but also on proteins such as ␤-catenin that bind to cadherin's intracellular tail. In 2010, Troyanovsky and colleagues developed a " tailless " cadherin mutant that could assemble junctions without binding to catenins (3), allowing the researchers to focus on the extracellular domain's contribution. Structural models suggest that extracellular cad-herin regions can form two types of dimers. The fi rst is a strand-swapped dimer in which each cad-herin inserts a tryptophan residue into a hydropho-bic pocket within their partner. Two cad-herins can also adopt a weaker confi gura-tion, known as an X dimer. Hong et al. made mutations to block each of these interaction modes in tailless cadherins (1). Surprisingly, when high-affi nity strand swapping was prevented—so that X di-merization was the only mode of interaction between cadherins—the adhesion proteins still formed junctions, albeit unstable ones with rapid turnover of individual cadherin molecules. On the other hand, tailless cad-herins unable to X dimerize formed extremely stable junctions. " These mutants formed junctions slowly, but once the cad-herins were integrated, they couldn't exit the junction, " Troyanovsky says. These observations were hard to interpret until a bio-physical study found that X dimerization is an intermediate step in the cadherin strand-swapping process (4). Cadherin mutants unable to form X dimers would therefore be expected to have very slow strand-swap di-mer assembly and disassembly and, consequently , slow adherens junction dynamics. " It looked like everything made sense, " says Troyanovsky, " except that expression of the X-dimer mutants also infl uences the behavior of endogenous cadherin present in the same cells. " Wild-type cad-herin molecules also formed junctions slowly in the presence of the X-dimerization mutant. Why would this be the case if endogenous cadherin could still …