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Volume EM reveals three-dimensional architecture of the desmosome in epithelial cells and tissue models
Insights
Three-dimensional imaging reveals novel details of desmosome structure in epithelial cells, including unique "holes" in their outer dense plaque. This provides a new understanding of these crucial cell adhesion structures.
Area of Science:
- Cell Biology
- Structural Biology
- Biophysics
Background:
- Desmosomes are vital cell-cell adhesion junctions in epithelial and cardiac tissues.
- They anchor to intermediate filaments, ensuring tissue mechanical integrity.
- Previous understanding relied on limited 2D electron microscopy data.
Purpose of the Study:
- To investigate the 3D ultrastructure of desmosomes in human epithelial cells.
- To identify variations in desmosome organization at different junction types.
- To describe novel structural features of desmosomes.
Main Methods:
- Focused ion beam scanning electron microscopy (FIB-SEM) for high-resolution 3D imaging.
- Analysis of desmosomes in A431, S1 human mammary epithelial cells, and human nasal airway epithelial cells.
- Quantitative analysis of desmosome size, shape, and organization from volume EM datasets.
Main Results:
- Detailed 3D ultrastructure of desmosomes in human epithelial cells.
- Observed variations in desmosome size, shape, and organization.
- Discovered discontinuities or "holes" in the desmosome outer dense plaque, a novel finding.
Conclusions:
- This study provides the first comprehensive 3D description of epithelial desmosomes.
- Novel structural features, like plaque discontinuities, challenge existing models.
- Further research is needed on desmosome dynamics in morphogenesis and disease.
Abstract:
Desmosomes are a type of cell-cell adhesive junction present in cardiac tissue and epithelial tissues such as the epidermis. These intercellular junctions anchor to the intermediate filament cytoskeleton, providing mechanical integrity to the tissues in which they reside. Our understanding of desmosome architecture has largely been influenced by observations of two-dimensional images obtained through conventional electron microscopy. Here, using focused ion beam scanning electron microscopy, we report the three-dimensional ultrastructure of desmosomes in A431 and S1 human mammary epithelial cells. We also reveal differences in desmosome ultrastructure at homo- and heterotypic junctions of human nasal airway epithelial cells. Quantitative analyses of these volume EM datasets reveal variations in desmosome size, shape, and organization. Importantly, we report the presence of discontinuities or "holes" within the desmosome outer dense plaque, a novel feature that is observed in either one or both halves of a desmosome. This study provides the first comprehensive description of the epithelial desmosome as a three-dimensional structure, and emphasizes the need to investigate the effects of dynamic morphogenetic processes and disease states on desmosome ultrastructure.
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