Desmosomes undergo dynamic architectural changes during assembly and maturation

• DOI: 10.1080/21688370.2021.2017225
• Publication Date: 2022-01-05T09:26:16Z
• Authors: Reena R. Beggs; Tejeshwar C. Rao; William F. Dean; Andrew P. Kowalczyk; Alexa L. Mattheyses
• Keywords: Desmoplakin; Desmosome; Plakoglobin; Desmoglein

Desmosomes are macromolecular cell-cell junctions critical for maintaining adhesion and resisting mechanical stress in epithelial tissue. Desmosome assembly the relationship between maturity molecular architecture not well understood. To address this, we employed a calcium switch assay to synchronize followed by quantification of desmosome nanoscale organization using direct Stochastic Optical Reconstruction Microscopy (dSTORM). We found that desmoplakin rod/C-terminal junction changed over course maturation, as indicated decrease plaque-to-plaque distance, while plaque length increased. In contrast, N-terminal domain plakoglobin (plaque-to-plaque distance) were constant throughout maturation. This structural rearrangement was concurrent with maturation measured E-cadherin exclusion increased adhesive strength. Using two-color dSTORM, showed number individual containing went down increasing time high Ca2+, they maintained wider distance. indicates state desmosomes can be identified their architectural organization. confirmed these changes another model assembly, cell migration. migrating cells, closest scratch where assembling, shorter, enriched, had distances compared away from wound edge. Key results demonstrated three lines representing simple, transitional, stratified epithelia. Together, data suggest there is set programs hypothesize may contributing mechanism regulating