期刊
TISSUE BARRIERS
卷 10, 期 4, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/21688370.2021.2017225
关键词
desmosome; dSTORM; super-resolution; microscopy; junction; desmoplakin; epithelia
资金
- National Institute of Arthritis and Musculoskeletal and Skin Diseases [R01AR072697, T32CA183926, P30CA013148]
The study revealed structural rearrangements in desmosomes during maturation, with some parts of desmoplakin showing decreased plaque-to-plaque distance and increased plaque length, while other parts remained constant. This structural reorganization was correlated with desmosome maturation and adhesive strength, suggesting that the architectural organization of desmosomes can indicate their maturation state. Additionally, migrating cells showed differences in desmosome structure compared to those forming at the wound edge, highlighting the impact of cell migration on desmosome assembly and architecture.
Desmosomes are macromolecular cell-cell junctions critical for maintaining adhesion and resisting mechanical stress in epithelial tissue. Desmosome assembly and the relationship between maturity and molecular architecture are not well understood. To address this, we employed a calcium switch assay to synchronize assembly followed by quantification of desmosome nanoscale organization using direct Stochastic Optical Reconstruction Microscopy (dSTORM). We found that the organization of the desmoplakin rod/C-terminal junction changed over the course of maturation, as indicated by a decrease in the plaqueto-plaque distance, while the plaque length increased. In contrast, the desmoplakin N-terminal domain and plakoglobin organization (plaque-to-plaque distance) were constant throughout maturation. This structural rearrangement of desmoplakin was concurrent with desmosome maturation measured by E-cadherin exclusion and increased adhesive strength. Using twocolor dSTORM, we showed that while the number of individual E-cadherin containing junctions went down with the increasing time in high Ca2+, they maintained a wider desmopla kin rod/C-terminal plaque-to-plaque distance. This indicates that the maturation state of individual desmosomes can be identified by their architectural organization. We confirmed these architectural changes in another model of desmosome assembly, cell migration. Desmosomes in migrating cells, closest to the scratch where they are assembling, were shorter, E-cadherin enriched, and had wider desmoplakin rod/C-terminal plaque-to-plaque distances compared to desmosomes away from the wound edge. Key results were demonstrated in three cell lines representing simple, transitional, and stratified epithelia. Together, these data suggest that there is a set of architectural programs for desmosome maturation, and we hypothesize that desmoplakin architecture may be a contributing mechanism to regulating adhesive strength.
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