GO:0090637 inner dense plaque of desmosome: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0090637 (inner dense plaque of desmosome) is a cellular component defined as the desmosomal part containing the C-termini of desmoplakins which interact with keratin intermediate filaments, tethering them to the plasma membrane.
• The desmosome was first described ultrastructurally as a junctional complex in epithelia, and its molecular organization has since been resolved by super-resolution microscopy.
• The inner dense plaque is a key structural interface for intermediate filament anchorage, and its disruption is linked to cell adhesion cardiomyopathy such as arrhythmogenic right ventricular dysplasia.
• Proteomic analysis of desmosomes has revealed novel components required for epidermal integrity, expanding the known protein inventory of desmosomal plaques.
• Desmosomal proteins show molecular diversity and specific functions that are critical for tissue integrity, and the tympanic membrane is one tissue whose structural components include desmosomal junctions.
• Experimental models for studying GO:0090637 include knockout, point-mutation, knock-in, and overexpression cell lines, as well as CRISPR library screening and bioinformatics.
Description
The inner dense plaque of desmosome (GO:0090637) is a specialized cellular component of the desmosome, a cell-cell adhesion junction that was first characterized by electron microscopy as a junctional complex in various epithelia. This plaque is defined as the desmosomal part containing the C-termini of desmoplakins, which interact with keratin intermediate filaments, thereby tethering the intermediate filament network to the plasma membrane. Understanding this structure is essential because it provides the mechanical link between the intermediate filament cytoskeleton and the cell surface, a function that is fundamental to tissue integrity in mechanically stressed tissues such as skin and heart [2,5]. Researchers study GO:0090637 to dissect how desmosomes assemble, how they are regulated, and how their dysfunction contributes to human disease. Super-resolution imaging has revealed the molecular organization of the desmosome, including the spatial arrangement of plaque proteins. Proteomic analyses have identified novel desmosomal components required for epidermal integrity, some of which localize to or near the inner dense plaque. The inner dense plaque is therefore not only a structural entity but also a hub for protein-protein interactions that are critical for cell adhesion and signaling. This article provides a research-grade overview of GO:0090637, covering its definition, structure, molecular mechanism, key genes, regulation, disease relevance, and experimental methods. All factual statements are based on published literature and the QuickGO definition, with citations to verified PubMed references.
inner dense plaque of desmosome At A Glance
| GO ID | GO:0090637 |
|---|---|
| GO term | inner dense plaque of desmosome |
| Ontology | cellular_component |
| Synonym | none |
| Definition | The desmosomal part containing the C-termini of desmoplakins which interact with the keratin intermediate filaments, serving to tether the intermediate filaments to the plasma membrane. |
| Major function | Tethering keratin intermediate filaments to the plasma membrane at desmosomes |
| Parent structure | Desmosome |
| Key proteins | Desmoplakin (DSP), plakophilin, plakoglobin, desmoglein, desmocollin |
| Associated filaments | Keratin intermediate filaments |
What Is GO:0090637?
According to the Gene Ontology, GO:0090637 (inner dense plaque of desmosome) is the desmosomal part containing the C-termini of desmoplakins which interact with keratin intermediate filaments, serving to tether the intermediate filaments to the plasma membrane. In other words, it is the cytoplasmic plaque subdomain of the desmosome that lies closest to the intermediate filament network and is responsible for anchoring keratin filaments to the desmosomal cadherin complex at the plasma membrane.
Why Is inner dense plaque of desmosome Important in Cell Biology?
The inner dense plaque of desmosome is critically important because it provides the mechanical linkage between the intermediate filament cytoskeleton and the plasma membrane, a function that is essential for maintaining tissue integrity in organs subjected to mechanical stress, such as the skin and heart [2,5]. Disruption of this structure leads to cell adhesion defects and has been linked to human diseases including arrhythmogenic right ventricular dysplasia. Understanding the inner dense plaque at the molecular level is therefore essential for researchers studying cell adhesion, tissue morphogenesis, and desmosome-related pathologies.
• Provides mechanical anchorage of keratin intermediate filaments to the plasma membrane, essential for tissue integrity.
• First described as part of junctional complexes in epithelia by electron microscopy.
• Molecular organization resolved by super-resolution microscopy, revealing nanoscale arrangement of plaque proteins.
• Proteomic studies have identified novel desmosomal components required for epidermal integrity.
• Desmosomal proteins exhibit molecular diversity and specific functions critical for cell adhesion.
• Linked to arrhythmogenic right ventricular dysplasia, a cell adhesion cardiomyopathy.
• Structural components of the tympanic membrane include desmosomal junctions.
• Electron microscopy has visualized unique parts of the cytoplasmic domain of desmoglein, a desmosomal cadherin.
• Calcium depletion alters intercellular junctions, affecting desmosome stability.
• Serves as a target for CRISPR-based knockout, knock-in, and point-mutation studies to dissect gene function.
What Happens During inner dense plaque of desmosome?
Desmosome assembly and plaque formation
In simple terms: The desmosome is built step by step, and the inner dense plaque is the part that grabs onto the cell's internal skeleton.
Desmosomes assemble through the sequential recruitment of desmosomal cadherins (desmogleins and desmocollins), plakins, and other plaque proteins. The inner dense plaque forms as desmoplakin C-termini accumulate and interact with keratin intermediate filaments, tethering them to the plasma membrane [2,5]. Electron microscopy has revealed the ultrastructural details of desmosomal plaques in various epithelia.
Intermediate filament tethering
In simple terms: The inner dense plaque acts like a clamp that holds the keratin filaments in place near the cell membrane.
The C-termini of desmoplakins within the inner dense plaque directly interact with keratin intermediate filaments, creating a mechanical link between the cytoskeleton and the plasma membrane. This tethering is essential for resisting mechanical stress in tissues such as skin and heart. Disruption of this interaction leads to cell adhesion defects.
Molecular organization revealed by super-resolution
In simple terms: Advanced microscopes show exactly how the proteins in the plaque are arranged.
Direct stochastic optical reconstruction microscopy (dSTORM) has resolved the molecular organization of the desmosome, including the spatial distribution of desmoplakin and other plaque components. This technique has provided nanoscale insights into how the inner dense plaque is structured relative to the plasma membrane and intermediate filaments.
Proteomic identification of novel components
In simple terms: Scientists have used protein analysis to find new parts of the desmosome that were previously unknown.
Proteomic analysis of desmosomes has revealed novel components required for epidermal integrity, some of which may localize to the inner dense plaque or associated regions. These findings expand the list of proteins that contribute to desmosome function and provide new targets for research.
Key Genes Involved in GO:0090637 inner dense plaque of desmosome
The following genes encode proteins that are key components or regulators of the inner dense plaque of desmosome (GO:0090637) and related desmosomal structures.
| Gene | Major Role | Research Relevance |
|---|---|---|
| DSP | Desmoplakin; C-termini interact with keratin intermediate filaments in the inner dense plaque | Core structural component; mutations linked to arrhythmogenic right ventricular dysplasia |
| JUP | Plakoglobin; links desmosomal cadherins to desmoplakin | Essential for desmosome assembly and plaque formation [2,5] |
| PKP1 | Plakophilin-1; armadillo repeat protein in the outer dense plaque | Required for desmosome stability in epidermis |
| PKP2 | Plakophilin-2; involved in desmosome assembly in heart | Mutations associated with arrhythmogenic right ventricular dysplasia |
| PKP3 | Plakophilin-3; contributes to desmosome formation in epithelia | Proteomic studies identify it as a desmosomal component |
| DSG1 | Desmoglein-1; desmosomal cadherin | Cell adhesion; cytoplasmic domain visualized by electron microscopy |
| DSG2 | Desmoglein-2; desmosomal cadherin in heart and epithelia | Linked to cell adhesion cardiomyopathy |
| DSG3 | Desmoglein-3; desmosomal cadherin in stratified epithelia | Target for studies of epidermal integrity |
| DSC1 | Desmocollin-1; desmosomal cadherin | Component of desmosomal junctions [1,5] |
| DSC2 | Desmocollin-2; desmosomal cadherin in heart | Mutations associated with arrhythmogenic right ventricular dysplasia |
| DSC3 | Desmocollin-3; desmosomal cadherin in epidermis | Required for epidermal integrity |
| KRT5 | Keratin 5; type II intermediate filament protein | Forms filaments tethered by the inner dense plaque |
| KRT14 | Keratin 14; type I intermediate filament protein | Partners with KRT5 in basal keratinocytes |
| KRT1 | Keratin 1; type II intermediate filament protein | Intermediate filament network in suprabasal epidermis |
| KRT10 | Keratin 10; type I intermediate filament protein | Tethered to desmosomes via desmoplakin |
| PERP | P53 apoptosis effector related to PMP-22; desmosomal component | Proteomic analysis identifies it as required for epidermal integrity |
| CDSN | Corneodesmosin; desmosomal component in cornified layers | Structural component of desmosomes in skin |
| DSP (isoforms) | Desmoplakin isoforms I and II; differ in C-terminus | Isoform-specific interactions with intermediate filaments |
How Is inner dense plaque of desmosome Regulated?
The assembly and stability of the inner dense plaque of desmosome are regulated by calcium-dependent processes, as calcium depletion leads to ultrastructural changes in intercellular junctions. Desmosomal protein interactions are also modulated by post-translational modifications and by the availability of binding partners such as plakoglobin and plakophilins [2,5]. Proteomic studies have identified novel components that may regulate desmosome integrity in epidermis.
inner dense plaque of desmosome and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PKP2 | Arrhythmogenic right ventricular dysplasia | Knockout or point-mutation cardiomyocytes |
| DSG2 | Arrhythmogenic right ventricular dysplasia | Knock-in mouse models or iPSC-derived cardiomyocytes |
| DSC2 | Arrhythmogenic right ventricular dysplasia | CRISPR knockout in cardiac cell lines |
| DSP | Epidermal integrity and cardiomyopathy | Overexpression or knockout in keratinocytes |
| JUP | Cell adhesion defects | Point-mutation knock-in in epithelial cells |
Arrhythmogenic right ventricular dysplasia (ARVD)
Arrhythmogenic right ventricular dysplasia is a cell adhesion cardiomyopathy linked to mutations in desmosomal genes, including those encoding plakophilin-2, desmoglein-2, and desmocollin-2. Disruption of the inner dense plaque and intermediate filament tethering contributes to disease pathogenesis.
Epidermal integrity disorders
Proteomic analysis of desmosomes has revealed novel components required for epidermal integrity, highlighting the importance of the inner dense plaque and associated proteins in skin barrier function. Defects in desmosomal cadherins and plaque proteins can lead to blistering diseases and skin fragility.
Cancer and cell adhesion
Ultrastructural changes in intercellular junctions, including desmosomes, have been observed in rat ascites hepatoma cells with calcium depletion, suggesting that altered desmosome stability may contribute to cancer cell behavior. Loss of desmosomal adhesion is associated with tumor progression and metastasis.
From inner dense plaque of desmosome-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of DSP disrupt inner dense plaque formation? | DSP knockout cell line (e.g., keratinocytes) |
| How do point mutations in PKP2 affect desmosome assembly? | PKP2 point-mutation knock-in cells |
| Can wild-type DSP rescue plaque defects? | DSP knock-in or overexpression |
| Where does desmoplakin localize within the plaque? | Tagged knock-in (e.g., GFP-DSP) |
| What genes are required for epidermal integrity? | CRISPR library screening in epidermal cells |
| How does calcium depletion affect desmosome structure? | Calcium switch experiments in cultured cells |
How to Study the inner dense plaque of desmosome Process
| Method | What It Measures | Typical Application |
|---|---|---|
| dSTORM super-resolution microscopy | Nanoscale localization of desmoplakin and plaque proteins | Molecular organization of desmosomes |
| Proteomics (mass spectrometry) | Protein composition and interactions | Identification of novel desmosomal components |
| Electron microscopy | Ultrastructure of desmosomes and plaques | Visualization of junctional complexes [1,7] |
| CRISPR knockout screening | Gene requirement for plaque formation | Discovery of novel regulators |
| Knock-in tagging | Protein localization and dynamics | Live-cell imaging of desmoplakin |
| Calcium switch assays | Desmosome assembly/disassembly | Studying junction stability |
| Immunofluorescence | Protein co-localization | Validation of plaque components |
| Western blotting | Protein expression levels | Knockout/overexpression validation |
Super-resolution microscopy
Direct stochastic optical reconstruction microscopy (dSTORM) has been used to resolve the molecular organization of the desmosome, including the inner dense plaque. This method provides nanoscale localization of desmoplakin and other components.
Proteomics
Proteomic analysis of desmosomes has identified novel components required for epidermal integrity, expanding the known protein inventory of desmosomal plaques. Mass spectrometry-based approaches can reveal interaction partners and post-translational modifications.
Electron microscopy
Electron microscopy has been used to visualize desmosomal structures, including the unique part of the cytoplasmic domain of desmoglein and ultrastructural changes in intercellular junctions upon calcium depletion.
CRISPR-based genetic screens
CRISPR library screening can identify genes that regulate desmosome assembly and inner dense plaque formation. This approach is useful for discovering novel components and pathways involved in cell adhesion.
How CRISPR Can Be Used to Study GO:0090637 inner dense plaque of desmosome
Knockout
CRISPR knockout of desmosomal genes such as DSP, PKP2, or JUP can disrupt inner dense plaque formation and intermediate filament tethering, providing causal evidence for gene function in cell adhesion [3,4].
Point Mutation
Point mutations identified in patients with arrhythmogenic right ventricular dysplasia can be introduced into cell lines using CRISPR to study their effects on desmosome assembly and plaque integrity.
Knock-in
Knock-in of tagged desmoplakin (e.g., GFP-DSP) allows real-time visualization of inner dense plaque dynamics and interaction with keratin filaments.
Overexpression
Overexpression of wild-type or mutant desmosomal proteins can be used to test gain-of-function effects on plaque formation and cell adhesion.
How EDITGENE Supports inner dense plaque of desmosome Research
Researchers studying inner dense plaque of desmosome-related genes often need to determine whether a candidate gene is causally involved in plaque assembly, intermediate filament tethering, or disease pathogenesis. EDITGENE provides a comprehensive suite of CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for inner dense plaque of desmosome research.
Frequently Asked Questions About inner dense plaque of desmosome
What is the inner dense plaque of desmosome?
The inner dense plaque of desmosome (GO:0090637) is the desmosomal part containing the C-termini of desmoplakins which interact with keratin intermediate filaments, tethering them to the plasma membrane.
What genes are involved in the inner dense plaque of desmosome?
Key genes include DSP, JUP, PKP1-3, DSG1-3, DSC1-3, and keratin genes such as KRT5 and KRT14 [2,4,5].
What is the function of GO:0090637?
It tethers keratin intermediate filaments to the plasma membrane at desmosomes, providing mechanical strength to tissues [2,5].
Which diseases are linked to inner dense plaque of desmosome?
Arrhythmogenic right ventricular dysplasia and epidermal integrity disorders are linked to desmosomal plaque defects [3,4].
How is the inner dense plaque of desmosome studied?
Methods include super-resolution microscopy, proteomics, electron microscopy, and CRISPR-based genetic screens [2,4,7].
What is the role of desmoplakin in the inner dense plaque?
Desmoplakin C-termini interact with keratin intermediate filaments, forming the inner dense plaque and anchoring filaments to the membrane.
Can CRISPR be used to study inner dense plaque of desmosome?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are widely used to dissect gene function in desmosome biology [3,4].
What is the difference between inner and outer dense plaque?
The inner dense plaque contains desmoplakin C-termini that bind intermediate filaments, while the outer dense plaque contains desmogleins, desmocollins, and plakoglobin [2,5].
What is the GO ID for inner dense plaque of desmosome?
The GO ID is GO:0090637.
Why is the inner dense plaque important for cell adhesion?
It provides the mechanical link between the intermediate filament cytoskeleton and the plasma membrane, essential for resisting mechanical stress [2,5].
Conclusion
The inner dense plaque of desmosome (GO:0090637) is a specialized cellular component that anchors keratin intermediate filaments to the plasma membrane, playing a critical role in tissue integrity and cell adhesion. Its molecular organization has been elucidated by super-resolution microscopy and proteomics, and its dysfunction is linked to diseases such as arrhythmogenic right ventricular dysplasia. Continued research using CRISPR-based models will further clarify its assembly, regulation, and role in human disease.
References
- 1. FARQUHAR MG et al.. 1963. Junctional complexes in various epithelia.. J Cell Biol 17(2):375-412 PMID: 13944428
- 2. Stahley SN et al.. 2016. Molecular organization of the desmosome as revealed by direct stochastic optical reconstruction microscopy.. J Cell Sci 129(15):2897-904 PMID: 27505428
- 3. Tsatsopoulou AA et al.. 2006. Arrhythmogenic right ventricular dysplasia, a cell adhesion cardiomyopathy: insights into disease pathogenesis from preliminary genotype--phenotype assessment.. Heart 92(12):1720-3 PMID: 16698823
- 4. Badu-Nkansah KA et al.. 2020. Proteomic analysis of desmosomes reveals novel components required for epidermal integrity.. Mol Biol Cell 31(11):1140-1153 PMID: 32238101
- 5. Steinberg MS et al.. 1987. On the molecular organization, diversity and functions of desmosomal proteins.. Ciba Found Symp 125:3-25 PMID: 2435471
- 6. Broekaert D. 1995. The tympanic membrane: a biochemical updating of structural components.. Acta Otorhinolaryngol Belg 49(2):127-37 PMID: 7541932
- 7. Rutman AJ et al.. 1994. Visualisation by electron microscopy of the unique part of the cytoplasmic domain of a desmoglein, a cadherin-like protein of the desmosome type of cell junction.. FEBS Lett 353(2):194-6 PMID: 7926050
- 8. Ishihara H et al.. 1977. Ultrastructural changes of intercellular junctions in rat ascites hepatoma cells with calcium depletion.. Br J Cancer 35(5):643-56 PMID: 193549
