Desmosomal Cadherin Tension Loss in Pemphigus Vulgaris Mediated by the Inhibition of Active RhoA at Cell-Cell Adhesions

Authors

• Xiaowei Jin, University of Nebraska-Lincoln
• Jordan Rosenbohm, University of Nebraska-Lincoln
• Eunju Kim, University of Nebraska-Lincoln
• Bahareh Tajvidi Safa, University of Nebraska-Lincoln and Michigan State University
• Amir Ostadi Moghaddam, University of Nebraska-Lincoln and Michigan State University
• Kristina Seiffert-Sinha, SUNY University at Buffalo
• Merced Leiker, SUNY University at Buffalo
• Elijah Jones, Michigan State University
• Haiwei Zhai, University of Nebraska-Lincoln
• Sindora R. Baddam, SUNY University at Buffalo
• Grayson Minnick, University of Nebraska-Lincoln
• Yucheng Huo, Nanyang Technological University, Singapore
• James K. Wahl III, University of Missouri-Kansas City
• Fanben Meng, University of Nebraska-Lincoln
• Changjin Huang, Nanyang Technological University, Singapore
• Jung Yul Lim, University of Nebraska-Lincoln
• Daniel E. Conway, The Ohio State University and The Ohio State University and Arthur G. James Comprehensive Cancer CenterFollow
• Animesh A. Sinha, SUNY University at BuffaloFollow
• Ruiguo Yang, University of Nebraska-Lincoln and Michigan State University and SUNY University at BuffaloFollow

Document Type

Article

Date of this Version

2025

Citation

iScience (2025) 28: 113081

doi: 10.1016/j.isci.2025.113081

Comments

Open access

License: CC BY-NC-ND 4.0

Abstract

Autoantibody binding to keratinocyte surface antigens, primarily desmoglein 3 (Dsg3) in the desmosome, leads to dissociation of cell-cell adhesions in pemphigus vulgaris. Much of the biophysical transformations after antibody binding remain underexplored. It is unclear how tensions in desmosomes and cell-cell adhesion structures change in response to antibodies, and how the altered tensional states translate to cellular responses. Here, using fluorescence resonance energy transfer-based tension sensors and traction force microscopy, we observed tension loss at Dsg3 and the entire cell-cell adhesion after antibody binding, along with potentially compensatory increase in junctional traction force at cell-extracellular matrix adhesions. Our data also indicate that this tension loss is mediated by RhoA inhibition at cell-cell contacts and can be partially restored by altering cell contractility. Collectively, these findings shed light on the biophysical mechanisms governing cell-cell interactions under autoimmune conditions, and may lead to therapies aimed at restoring tensional balance at cell-cell adhesions.