E-cadherin binds to desmoglein to facilitate desmosome assembly

  1. Omer Shafraz
  2. Matthias Rübsam
  3. Sara N Stahley
  4. Amber Caldara
  5. Andrew P Kowalczyk
  6. Carien M Niessen
  7. Sanjeevi Sivasankar  Is a corresponding author
  1. Iowa State University, United States
  2. University of Cologne, Germany
  3. 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

  1. Omer Shafraz

    Department of Physics and Astronomy, Iowa State University, Ames, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Matthias Rübsam

    Department of Dermatology, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Sara N Stahley

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Amber Caldara

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Andrew P Kowalczyk

    Department of Cell Biology, Emory University School of Medicine, Atlanta, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Carien M Niessen

    Department of Dermatology, University of Cologne, Cologne, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Sanjeevi Sivasankar

    Department of Physics and Astronomy, Iowa State University, Ames, United States
    For correspondence
    sivasank@iastate.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2593-0477

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

  1. William I Weis, Stanford University Medical Center, United States

Publication history

  1. Received: April 17, 2018
  2. Accepted: July 10, 2018
  3. Accepted Manuscript published: July 12, 2018 (version 1)
  4. 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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  1. Omer Shafraz
  2. Matthias Rübsam
  3. Sara N Stahley
  4. Amber Caldara
  5. Andrew P Kowalczyk
  6. Carien M Niessen
  7. Sanjeevi Sivasankar
(2018)
E-cadherin binds to desmoglein to facilitate desmosome assembly
eLife 7:e37629.
https://doi.org/10.7554/eLife.37629

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