GO:0090136 epithelial cell-cell adhesion: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0090136 (epithelial cell-cell adhesion) is defined as the attachment of an epithelial cell to another epithelial cell via adhesion molecules.
• Desmosomes are major adhesive junctions that mediate strong epithelial cell-cell adhesion and are composed of desmosomal cadherins (desmogleins and desmocollins) linked to intermediate filaments via plakoglobin and desmoplakin.
• Epithelial cell-cell adhesion is dynamically regulated; for example, vaginal epithelial cells can modulate membrane adhesiveness to coordinate bacterial adhesion.
• Altering the physicochemical properties of substrates, such as crosslinker content in silicone hydrogel materials, can tune corneal epithelial cell adhesive strength.
• Bioadhesive properties of nanoparticles and surface topographies influence epithelial cell adhesion, which is relevant for drug delivery and tissue engineering [5,7].
• Research on epithelial cell-cell adhesion employs knockout, knock-in, and overexpression models to dissect gene function in adhesion complexes.
Description
Epithelial cell-cell adhesion (GO:0090136) is a fundamental biological process that enables epithelial cells to attach to one another through specialized adhesion molecules. This process is critical for maintaining tissue integrity, forming barriers, and coordinating collective cell behaviors in development and homeostasis. Dysregulation of epithelial cell-cell adhesion contributes to various pathologies, including cancer and inflammatory diseases. Understanding the molecular components and regulatory mechanisms of epithelial cell-cell adhesion is essential for researchers in cell biology, tissue engineering, and drug delivery [3,5,7]. This article provides a comprehensive overview of the ontology term GO:0090136, its associated genes, experimental models, and research methodologies, based on authoritative QuickGO data and verified PubMed literature.
epithelial cell-cell adhesion At A Glance
| GO ID | GO:0090136 |
|---|---|
| GO term | epithelial cell-cell adhesion |
| Ontology | biological_process |
| Synonym | None |
| Major function | Attachment of epithelial cells to one another via adhesion molecules |
| Key molecules | Desmosomal cadherins (desmogleins, desmocollins), plakoglobin, desmoplakin, intermediate filaments |
| Associated cellular structures | Desmosomes, adherens junctions, tight junctions |
| Regulatory examples | Membrane adhesiveness modulation by epithelial cells |
| Experimental modulation | Substrate crosslinker content affects corneal epithelial cell adhesive strength |
What Is GO:0090136?
GO:0090136, epithelial cell-cell adhesion, is defined as the attachment of an epithelial cell to another epithelial cell via adhesion molecules. This process encompasses the physical and molecular interactions that link adjacent epithelial cells, primarily through specialized junctional complexes such as desmosomes, adherens junctions, and tight junctions. It is a biological process that ensures tissue cohesion and barrier function.
Why Is epithelial cell-cell adhesion Important in Cell Biology?
Epithelial cell-cell adhesion is essential for the structural integrity of epithelial tissues and for the formation of protective barriers. It plays a central role in embryonic development, wound healing, and tissue homeostasis, and its disruption is a hallmark of cancer progression and metastasis. Moreover, understanding epithelial cell-cell adhesion is crucial for designing biomaterials and drug delivery systems that interact with epithelial surfaces [3,5,7].
• Maintains tissue architecture and barrier function in epithelial organs.
• Enables collective cell migration and coordinated responses during development and repair.
• Dysregulation leads to loss of cell polarity and increased invasiveness in cancer.
• Influences bacterial adhesion and colonization on epithelial surfaces.
• Critical for corneal epithelial wound healing and integration with biomaterials.
• Affects drug delivery by modulating nanoparticle bioadhesion to epithelial cells.
• Surface topography and chemistry can be engineered to control epithelial cell adhesion.
• Provides targets for therapeutic intervention in inflammatory and infectious diseases.
• Serves as a model system for studying cell adhesion mechanisms.
• Relevant for tissue engineering and regenerative medicine applications [3,5].
What Happens During epithelial cell-cell adhesion?
Initiation of Adhesion
In simple terms: Epithelial cells first make contact with each other using adhesion molecules on their surfaces.
The initiation of epithelial cell-cell adhesion involves the engagement of adhesion molecules, such as desmosomal cadherins, between neighboring cells. This initial contact is often mediated by calcium-dependent interactions and can be influenced by the local environment, including membrane adhesiveness.
Formation of Desmosomes
In simple terms: Desmosomes are strong glue-like structures that hold epithelial cells together.
Desmosomes are major adhesive junctions that form when desmosomal cadherins (desmogleins and desmocollins) on adjacent cells bind to each other. These cadherins are linked intracellularly to plakoglobin and desmoplakin, which in turn connect to intermediate filaments, providing mechanical strength.
Maturation and Reinforcement
In simple terms: The adhesion structures become stronger and more organized over time.
After initial contact, desmosomes mature by recruiting additional proteins and organizing into dense plaques. This maturation is essential for withstanding mechanical stress and maintaining tissue integrity.
Dynamic Regulation
In simple terms: Cells can adjust how sticky they are to control adhesion.
Epithelial cell-cell adhesion is not static; cells can regulate membrane adhesiveness in response to external cues, as shown in vaginal epithelial cells coordinating bacterial adhesion. This dynamic regulation allows tissues to adapt to changing conditions.
Key Genes Involved in GO:0090136 epithelial cell-cell adhesion
The following genes and proteins are key players in epithelial cell-cell adhesion, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| DSG1 | Desmoglein 1, a desmosomal cadherin | Component of desmosomes; target for studying adhesion strength |
| DSG3 | Desmoglein 3, a desmosomal cadherin | Involved in epithelial adhesion; autoantigen in pemphigus |
| DSC1 | Desmocollin 1, a desmosomal cadherin | Mediates cell-cell adhesion in desmosomes |
| DSC2 | Desmocollin 2, a desmosomal cadherin | Contributes to desmosome formation |
| DSC3 | Desmocollin 3, a desmosomal cadherin | Important for epidermal adhesion |
| JUP | Plakoglobin, links cadherins to desmoplakin | Key adaptor in desmosomes and adherens junctions |
| DSP | Desmoplakin, links desmosomes to intermediate filaments | Essential for desmosome function |
| KRT5 | Keratin 5, intermediate filament protein | Provides mechanical support to desmosomes |
| KRT14 | Keratin 14, intermediate filament protein | Pairs with KRT5 in basal epithelial cells |
| CDH1 | E-cadherin, adherens junction protein | Mediates calcium-dependent adhesion |
| CTNNB1 | Beta-catenin, links E-cadherin to actin | Dual role in adhesion and signaling |
| CTNNA1 | Alpha-catenin, links beta-catenin to actin | Stabilizes adherens junctions |
| PKP1 | Plakophilin 1, desmosomal plaque protein | Regulates desmosome assembly |
| PKP2 | Plakophilin 2, desmosomal plaque protein | Involved in desmosome stability |
| PKP3 | Plakophilin 3, desmosomal plaque protein | Modulates adhesion in epithelia |
| DSP | Desmoplakin, cytolinker protein | Connects desmosomes to intermediate filaments |
| JUP | Plakoglobin, armadillo protein | Also known as gamma-catenin |
How Is epithelial cell-cell adhesion Regulated?
Epithelial cell-cell adhesion is regulated at multiple levels, including the expression and post-translational modification of adhesion molecules, as well as environmental factors. For instance, vaginal epithelial cells can regulate membrane adhesiveness to coordinate bacterial adhesion, indicating active modulation of adhesion properties. Additionally, substrate properties such as crosslinker content in silicone hydrogel materials can tune corneal epithelial cell adhesive strength, highlighting the influence of extracellular matrix and material surface on adhesion. The bioadhesive properties of nanoparticles also affect epithelial cell adhesion, which is relevant for drug delivery.
epithelial cell-cell adhesion and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| DSG1 | Pemphigus foliaceus | Knockout or point mutation in keratinocytes |
| DSG3 | Pemphigus vulgaris | Knockout mouse models |
| DSP | Arrhythmogenic right ventricular cardiomyopathy | Knock-in mouse models |
| JUP | Naxos disease | Knockout or point mutation in epithelial cells |
| CDH1 | Hereditary diffuse gastric cancer | Knockout or overexpression in gastric organoids |
Cancer and Metastasis
Loss of epithelial cell-cell adhesion is a critical step in cancer progression, enabling cells to detach from the primary tumor and invade surrounding tissues. Downregulation of desmosomal components and E-cadherin is frequently observed in carcinomas and correlates with poor prognosis.
Autoimmune Blistering Diseases
Autoantibodies against desmogleins disrupt desmosomal adhesion, leading to skin blistering diseases such as pemphigus vulgaris and pemphigus foliaceus. This highlights the importance of desmosomal cadherins in maintaining epithelial integrity.
Infectious Diseases
Pathogens can exploit or disrupt epithelial cell-cell adhesion to colonize or invade tissues. For example, vaginal epithelial cells regulate membrane adhesiveness to coordinate bacterial adhesion, which may influence susceptibility to infections.
Corneal Wound Healing
Corneal epithelial cell adhesive strength is critical for wound healing and integration with biomaterials. Varying crosslinker content in silicone hydrogel materials can modulate this adhesion, which has implications for contact lens design and ocular therapeutics.
From epithelial cell-cell adhesion-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate desmosome assembly? | Knockout of gene X in epithelial cell lines |
| How does a point mutation in DSG3 affect adhesion? | Point mutation knock-in in keratinocytes |
| Can overexpression of DSC2 enhance adhesion? | Overexpression of DSC2 in epithelial cells |
| What is the role of plakoglobin in adhesion? | Knockout of JUP in mouse models |
| How does substrate stiffness affect adhesion? | In vitro culture on tunable substrates |
| Does nanoparticle bioadhesion alter epithelial adhesion? | In vitro epithelial cell monolayers with nanoparticles |
How to Study the epithelial cell-cell adhesion Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Cell adhesion assay | Strength of cell-cell or cell-substrate attachment | Evaluating effects of gene knockout on adhesion |
| Immunofluorescence | Localization of adhesion proteins | Visualizing desmosome formation |
| Western blot | Protein expression levels | Quantifying desmoglein expression |
| Proteomics | Protein interactions and modifications | Identifying novel adhesion complex components |
| CRISPR knockout | Loss-of-function effects | Determining gene requirement for adhesion |
| CRISPR knock-in | Gain-of-function or tagging | Studying mutant adhesion proteins |
| Overexpression | Increased protein levels | Assessing sufficiency of a gene in adhesion |
| Bioinformatics | Gene ontology and pathway analysis | Interpreting omics data related to adhesion |
Cell Adhesion Assays
Cell adhesion assays measure the strength of attachment between epithelial cells or between cells and substrates. These assays can be used to evaluate the effects of genetic modifications or environmental factors on epithelial cell-cell adhesion [3,5].
Immunofluorescence Microscopy
Immunofluorescence microscopy visualizes the localization and organization of adhesion proteins, such as desmogleins and desmoplakin, at cell-cell junctions. This method is essential for assessing desmosome formation and maturation.
Western Blotting and Proteomics
Western blotting and proteomics quantify the expression levels of adhesion molecules and identify post-translational modifications. These techniques help elucidate regulatory mechanisms underlying epithelial cell-cell adhesion.
CRISPR-Cas9 Genome Editing
CRISPR-Cas9 genome editing enables the creation of knockout, knock-in, and point mutation models to study the function of specific genes in epithelial cell-cell adhesion. This approach provides causal insights into gene roles.
How CRISPR Can Be Used to Study GO:0090136 epithelial cell-cell adhesion
Knockout
CRISPR knockout models are used to completely ablate the expression of genes involved in epithelial cell-cell adhesion, such as DSG3 or JUP, to determine their essential roles in desmosome formation and tissue integrity.
Point Mutation
Point mutation knock-in models introduce specific disease-associated mutations, such as those found in DSP or JUP, to study their impact on adhesion protein function and disease pathogenesis.
Knock-in
Knock-in models can be used to tag endogenous adhesion proteins with fluorescent markers or to express mutant versions under native regulatory control, enabling precise tracking of protein dynamics.
Overexpression
Overexpression models increase the levels of adhesion molecules, such as E-cadherin or desmocollins, to test whether enhanced adhesion can suppress invasive phenotypes or strengthen tissue barriers.
How EDITGENE Supports epithelial cell-cell adhesion Research
Researchers studying epithelial cell-cell adhesion-related genes often need to determine whether a candidate gene is causally involved in adhesion complex assembly, maintenance, or regulation. EDITGENE provides comprehensive CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for epithelial cell-cell adhesion research.
Frequently Asked Questions About epithelial cell-cell adhesion
What is GO:0090136?
GO:0090136 is the Gene Ontology term for epithelial cell-cell adhesion, defined as the attachment of an epithelial cell to another epithelial cell via adhesion molecules.
What genes are involved in epithelial cell-cell adhesion?
Key genes include desmogleins (DSG1, DSG3), desmocollins (DSC1-3), plakoglobin (JUP), desmoplakin (DSP), and E-cadherin (CDH1).
What are desmosomes?
Desmosomes are adhesive junctions composed of desmosomal cadherins linked to intermediate filaments, providing strong cell-cell adhesion in epithelia.
How is epithelial cell-cell adhesion regulated?
It is regulated by expression and modification of adhesion molecules, as well as environmental factors such as membrane adhesiveness and substrate properties [3,4].
What diseases are associated with defective epithelial cell-cell adhesion?
Diseases include pemphigus vulgaris, pemphigus foliaceus, arrhythmogenic right ventricular cardiomyopathy, and cancer metastasis.
How can I study epithelial cell-cell adhesion in the lab?
Common methods include cell adhesion assays, immunofluorescence, Western blotting, and CRISPR-Cas9 genome editing [3,8].
What CRISPR models are available for adhesion research?
Knockout, point mutation, knock-in, and overexpression models can be generated to study gene function in adhesion.
Does substrate stiffness affect epithelial cell adhesion?
Yes, varying crosslinker content in silicone hydrogel materials can tune corneal epithelial cell adhesive strength.
Can nanoparticles influence epithelial cell adhesion?
Yes, bioadhesive properties of nanoparticles can affect epithelial cell adhesion, which is relevant for drug delivery.
What is the role of plakoglobin in adhesion?
Plakoglobin (JUP) links desmosomal cadherins to desmoplakin and intermediate filaments, essential for desmosome function.
Conclusion
Epithelial cell-cell adhesion (GO:0090136) is a vital biological process that maintains tissue integrity and barrier function through specialized adhesion molecules such as desmosomal cadherins and their associated proteins. Its dysregulation is implicated in cancer, autoimmune diseases, and infectious pathologies [4,8]. Advances in CRISPR genome editing and bioinformatics are enabling deeper insights into the molecular mechanisms and regulatory networks governing epithelial cell-cell adhesion. EDITGENE provides a comprehensive suite of services to support researchers in this field.
References
- 3. Liu C et al.. 2020. Tuning corneal epithelial cell adhesive strength with varying crosslinker content in silicone hydrogel materials.. Transl Vis Sci Technol 9(6):3 PMID: 32821500
- 4. Younes JA et al.. 2016. Vaginal epithelial cells regulate membrane adhesiveness to co-ordinate bacterial adhesion.. Cell Microbiol 18(4):605-14 PMID: 26477544
- 5. Kidambi S et al.. 2007. Cell adhesion on polyelectrolyte multilayer coated polydimethylsiloxane surfaces with varying topographies.. Tissue Eng 13(8):2105-17 PMID: 17518734
- 7. Yoncheva K et al.. 2005. Bioadhesive properties of pegylated nanoparticles.. Expert Opin Drug Deliv 2(2):205-18 PMID: 16296748
- 8. Garrod D et al.. 2008. Desmosome structure, composition and function.. Biochim Biophys Acta 1778(3):572-87 PMID: 17854763
