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Elife. 2018 Jul 12;7. pii: e37629. doi: 10.7554/eLife.37629.

E-cadherin binds to desmoglein to facilitate desmosome assembly.

Author information

1
Department of Physics and Astronomy, Iowa State University, Ames, United States.
2
Department of Dermatology, Cologne Excellence Cluster on Cellular Stress Responses in Aging-associated Diseases, Center for Molecular Medicine Cologne, University of Cologne, Cologne, Germany.
3
Department of Cell Biology, Emory University School of Medicine, Atlanta, United States.
#
Contributed equally

Abstract

Desmosomes are adhesive junctions composed of two desmosomal cadherins: desmocollin (Dsc) and desmoglein (Dsg). Previous studies demonstrate that E-cadherin (Ecad), an adhesive protein that interacts in both trans (between opposing cells) and cis (on the same cell surface) conformations, facilitates desmosome assembly via an unknown mechanism. Here we use structure-function analysis to resolve the mechanistic roles of Ecad in desmosome formation. Using AFM force measurements, we demonstrate that Ecad interacts with isoform 2 of Dsg via a conserved Leu-175 on the Ecad cis binding interface. Super-resolution imaging reveals that Ecad is enriched in nascent desmosomes, supporting a role for Ecad in early desmosome assembly. Finally, confocal imaging demonstrates that desmosome assembly is initiated at sites of Ecad mediated adhesion, and that Ecad-L175 is required for efficient Dsg2 and desmoplakin recruitment to intercellular contacts. We propose that Ecad trans interactions at nascent cell-cell contacts initiate the recruitment of Dsg through direct cis interactions with Ecad which facilitates desmosome assembly.

KEYWORDS:

cadherins; cell adhesion; cell biology; desmosomes; none

PMID:
29999492
PMCID:
PMC6066328
DOI:
10.7554/eLife.37629
[Indexed for MEDLINE]
Free PMC Article

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