Different roles of cadherins in the assembly and structural integrity of the desmosome complex

Molly Lowndes, Sabyasachi Rakshit, Omer Shafraz, Nicolas Borghi, Robert M. Harmon, Kathleen J. Green, Sanjeevi Sivasankar, W. James Nelson*

*Corresponding author for this work

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Adhesion between cells is established by the formation of specialized intercellular junctional complexes, such as desmosomes. Desmosomes contain isoforms of two members of the cadherin superfamily of cell adhesion proteins, desmocollins (Dsc) and desmogleins (Dsg), but their combinatorial roles in desmosome assembly are not understood. To uncouple desmosome assembly from other cell-cell adhesion complexes, we used micro-patterned substrates of Dsc2aFc and/or Dsg2Fc and collagen IV; we show that Dsc2aFc, but not Dsg2Fc, was necessary and sufficient to recruit desmosome-specific desmoplakin into desmosome puncta and produce strong adhesive binding. Single-molecule force spectroscopy showed that monomeric Dsc2a, but not Dsg2, formed Ca2+-dependent homophilic bonds, and that Dsg2 formed Ca2+- independent heterophilic bonds with Dsc2a. A W2A mutation in Dsc2a inhibited Ca2+-dependent homophilic binding, similar to classical cadherins, and Dsc2aW2A, but not Dsg2W2A, was excluded from desmosomes in MDCK cells. These results indicate that Dsc2a, but not Dsg2, is required for desmosome assembly through homophilic Ca2+- and W2-dependent binding, and that Dsg2 might be involved later in regulating a switch to Ca2+-independent adhesion in mature desmosomes.

Original languageEnglish (US)
Pages (from-to)2339-2350
Number of pages12
JournalJournal of cell science
Volume127
Issue number10
DOIs
StatePublished - 2014

Keywords

  • Adhesion
  • Desmocollin
  • Desmoglein
  • Desmosome

ASJC Scopus subject areas

  • Cell Biology

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    Lowndes, M., Rakshit, S., Shafraz, O., Borghi, N., Harmon, R. M., Green, K. J., Sivasankar, S., & Nelson, W. J. (2014). Different roles of cadherins in the assembly and structural integrity of the desmosome complex. Journal of cell science, 127(10), 2339-2350. https://doi.org/10.1242/jcs.146316