Cooperativity between trans and cis interactions in cadherin-mediated junction formation

Yinghao Wu, Xiangshu Jin, Oliver Harrison, Lawrence Shapiro, Barry H. Honig, Avinoam Ben-Shaul

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Intercellullar junctions formed by cadherins, including desmosomes and adherens junctions, comprise two dimensional arrays of "trans" dimers formed between monomers emanating from opposing cell surfaces. Lateral "cis" interfaces between cadherins from the same cell surface have been proposed to play a role in cadherin clustering. Although the molecular details of cis interactions remain uncertain, they must define an anisotropic arrangement where binding is favorable only in certain orientations. Here we report Monte Carlo simulations performed on a 2D lattice constructed to account for the anisotropy in cadherin cis interactions. A crucial finding is that the "phase transition" between freely diffusing cadherinmonomers and dimers and a condensed ordered 2D junction formed by dimers alone is a cooperative process involving both trans and cis interactions. Moreover, cis interactions, despite being too weak to be measured in solution, are critical to the formation of an ordered junction structure. We discuss these results in light of available experimental information on cadherin binding free energies that are transformed from their bulk solution values to interaction energies on a 2D lattice.

Original languageEnglish (US)
Pages (from-to)17592-17597
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number41
DOIs
StatePublished - Oct 12 2010
Externally publishedYes

Keywords

  • Cell adhesion
  • Cis trans interfaces
  • Intercellular signaling

ASJC Scopus subject areas

  • General

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