E-cadherin binds to desmoglein to facilitate desmosome assembly
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.
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All data generated or analyzed during this study are included in the manuscript and supporting files.
Article and author information
Author details
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.
Reviewing Editor
- William I Weis, Stanford University Medical Center, United States
Version history
- Received: April 17, 2018
- Accepted: July 10, 2018
- Accepted Manuscript published: July 12, 2018 (version 1)
- Version of Record published: July 30, 2018 (version 2)
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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