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Originally published as MBC in Press, 10.1091/mbc.E07-01-0084 on August 29, 2007

Vol. 18, Issue 11, 4343-4352, November 2007

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Stable and Unstable Cadherin Dimers: Mechanisms of Formation and Roles in Cell AdhesionFormula

Regina B. Troyanovsky*, Oscar Laur{dagger}, and Sergey M. Troyanovsky{ddagger}

*Division of Dermatology, Washington University Medical School, St. Louis, MO 63110; {dagger}Department of Pathology and Laboratory Medicine, Emory University Medical School, Atlanta, GA 30322; and {ddagger}Department of Dermatology, Northwestern University, The Feinberg School of Medicine, Chicago, IL 60611

Submitted January 30, 2007; Revised August 10, 2007; Accepted August 17, 2007
Monitoring Editor: Ben Margolis

Numerous attempts to elucidate the strength of cadherin dimerization that mediates intercellular adhesion have produced controversial and inconclusive results. To clarify this issue, we compared E-cadherin dimerization on the surface of living cells with how the same process unfolds on agarose beads. In both cases, dimerization was monitored by the same site-specific cross-linking assay, greatly simplifying data interpretation. We showed that on the agarose surface under physiological conditions, E-cadherin produced a weak dimer that immediately dissociated after the depletion of calcium ions. However, either at pH 5 or in the presence of cadmium ions, E-cadherin produced a strong dimer that was unable to dissociate upon calcium depletion. Both types of dimers were W156-dependent. Remarkably, only the strong dimer was found on the surface of living cells. We also showed that the intracellular cadherin region, the clustering of which through catenins had been proposed as stabilizer of weak intercadherin interactions, was not needed, in fact, for cadherin junction assembly. Taken together, our data present convincing evidence that cadherin adhesion is based on high-affinity cadherin–cadherin interactions.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-01-0084) on August 29, 2007.

Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

Address correspondence to: Sergey Troyanovsky (s-troyanovsky{at}northwestern.edu)




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