E-cadherin binds to desmoglein to facilitate desmosome assembly
- Iowa State University, United States
- University of Cologne, Germany
- Emory University School of Medicine, United States
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 and cis 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.
Data availability
All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Sanjeevi Sivasankar
Funding
American Heart Association (12SDG9320022)
- Sanjeevi Sivasankar
National Institute of General Medical Sciences (R01GM121885)
- Sanjeevi Sivasankar
Deutsche Forschungsgemeinschaft (DFG SFB 829 A1)
- Carien M Niessen
Deutsche Forschungsgemeinschaft (DFG SFB 829 Z2)
- Carien M Niessen
Deutsche Forschungsgemeinschaft (DFG NI 1234/6-1)
- Carien M Niessen
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR048266)
- Andrew P Kowalczyk
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2018, Shafraz et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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E-cadherin binds to desmoglein to facilitate desmosome assembly
eLife 7:e37629.
https://doi.org/10.7554/eLife.37629
