GO:0098635 protein complex involved in cell-cell adhesion: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0098635 describes any protein complex that carries out part of the process of cell-cell adhesion, a cellular component annotation that groups together adhesion machines rather than a single molecular function [1,2,3].
• Cell-cell adhesion complexes are built from transmembrane adhesion receptors, cytoplasmic plaque proteins and cytoskeletal linkers that together mechanically couple neighbouring cells [1,3,6].
• The term covers evolutionarily ancient adhesion systems, from sponge histocompatibility complexes to yeast flocculation proteins and mammalian cadherin-catenin complexes [1,4,6].
• Adhesion complexes are dynamic: actin dynamics, phosphorylation and partner switching regulate their assembly, turnover and signalling output [3,5,8].
• Loss or rewiring of cell-cell adhesion complexes is linked to cancer invasion and metastasis, trophoblast differentiation and neuronal synapse organisation [6,7,8].
• CRISPR knockout, point-mutation, knock-in and overexpression models allow causal testing of individual components within these complexes [2,5,8].
Description
GO:0098635, protein complex involved in cell-cell adhesion, is a Gene Ontology cellular component term that captures any protein assembly capable of carrying out some part of the process of cell-cell adhesion [1,2,3]. Rather than describing a single molecule, the term groups the multi-protein machines that physically connect one cell to another and translate that connection into mechanical and signalling outputs [1,3,6]. These complexes range from the classical cadherin-catenin adhesion system of epithelia to neuronal adhesion complexes and even the flocculation machinery of yeast [4,6,8]. Because cell-cell adhesion underpins tissue architecture, barrier function and cell-fate signalling, researchers studying development, cancer and neurobiology routinely need to know which proteins belong to these complexes and how they assemble [3,6,7]. The QuickGO definition is deliberately broad: any protein complex that performs part of cell-cell adhesion qualifies, which makes the term a useful umbrella for annotation and for designing experiments that test complex composition and function [1,2,5]. Understanding GO:0098635 therefore means understanding how adhesion receptors, cytoplasmic adaptors and cytoskeletal linkers cooperate to hold cells together and to signal [1,3,8].
protein complex involved in cell-cell adhesion At A Glance
| GO ID | GO:0098635 |
|---|---|
| GO term | protein complex involved in cell-cell adhesion |
| Ontology | cellular_component |
| Synonym | None listed in QuickGO |
| Major function | Carrying out part of the process of cell-cell adhesion as a multi-protein assembly |
| Definition source | QuickGO definition: any protein complex capable of carrying out some part of cell-cell adhesion |
| Example systems | Cadherin-catenin complexes, neuronal adhesion complexes, sponge histocompatibility complexes, yeast flocculation complexes |
| Related processes | Cell-cell adhesion, actin dynamics, tissue architecture, signalling |
| Research relevance | Cancer invasion, trophoblast differentiation, neuronal adhesion and evolutionary cell adhesion studies |
What Is GO:0098635?
In plain terms, GO:0098635 is a cellular component category for protein complexes that do part of the job of sticking cells to each other. The official QuickGO definition states: any protein complex that is capable of carrying out some part of the process of cell-cell adhesion. It is not restricted to one adhesion system, so cadherin-catenin complexes, neuronal adhesion complexes and even microbial flocculation complexes can be annotated under this term [1,4,6]. The term sits under cellular_component and has no listed synonyms, so it should be cited by its exact ID and name [1,2,3].
Why Is protein complex involved in cell-cell adhesion Important in Cell Biology?
GO:0098635 matters because cell-cell adhesion complexes are the physical and signalling interface between neighbouring cells, and their composition determines whether a tissue stays coherent or becomes invasive [3,6,7]. The term provides a standard way to annotate and compare these complexes across species and experimental systems, from sponge histocompatibility to mammalian epithelia [1,4,6]. Because adhesion complexes are dynamic and regulated by actin dynamics and partner switching, they are also tractable targets for CRISPR-based perturbation and for mechanistic studies of disease [3,5,8].
• Defines the protein machines that execute cell-cell adhesion, a fundamental process in tissue formation and maintenance [1,3].
• Provides a common annotation for adhesion complexes across evolution, from sponges and yeast to mammals [1,4].
• Links adhesion to actin dynamics and cytoskeletal remodelling in epithelia.
• Is directly relevant to cancer invasion and metastasis through the E-cadherin cell-cell adhesion complex.
• Is relevant to trophoblast differentiation, invasion and experimental modulation of adhesion.
• Includes neuronal adhesion complexes that organise synapse-related signalling.
• Supports studies of signalling crosstalk, such as Merlin/NF2 interaction with the PAF complex.
• Enables CRISPR knockout, point-mutation, knock-in and overexpression experiments on individual complex components [2,5,8].
• Helps interpret proteomic and imaging data by grouping adhesion proteins into functional assemblies [2,3].
• Guides selection of disease models where adhesion complex integrity is a key variable [6,7].
What Happens During protein complex involved in cell-cell adhesion?
Initiation and receptor engagement
In simple terms: Adhesion starts when adhesion receptors on one cell meet their partners on another cell.
Cell-cell adhesion complexes begin to form when transmembrane adhesion receptors engage their counterparts on a neighbouring cell, creating the initial physical link [1,3,6]. In epithelial cadherin-catenin systems, this engagement is coupled to the actin cytoskeleton and is required for stable junction formation [3,6]. In neuronal contexts, C1QL3 promotes cell-cell adhesion by mediating complex formation between ADGRB3/BAI3 and neuronal pentraxins, illustrating that initiation can involve secreted or membrane-associated bridging factors.
Assembly of the cytoplasmic plaque
In simple terms: Once receptors touch, a protein plaque forms inside the cell to anchor and organise the adhesion.
Following receptor engagement, cytoplasmic plaque proteins assemble beneath the membrane to connect the adhesion receptor to the cytoskeleton and to signalling machinery [1,3,6]. Armadillo-repeat proteins such as Armc8 are evolutionarily conserved components that participate in cell-cell adhesion complexes through multiple molecular interactions. The composition of this plaque determines the mechanical strength and signalling output of the adhesion complex [2,3].
Cytoskeletal coupling and actin dynamics
In simple terms: The adhesion complex grabs the actin cytoskeleton so the cell can pull and hold on.
Actin dynamics are central to cell-cell adhesion in epithelia, where the adhesion complex is continuously remodelled as cells change shape and move. Cytoskeletal coupling allows adhesion complexes to resist mechanical force and to transmit signals that reorganise the actin network [3,6]. This coupling is not static; it is tuned by regulatory inputs that alter complex stability and turnover [3,5].
Regulation and signalling crosstalk
In simple terms: Adhesion complexes also send signals and can be rewired by other cellular pathways.
Adhesion complexes are signalling hubs as well as mechanical structures. Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex, showing that adhesion status can directly influence transcriptional regulatory machinery. In trophoblast cells, experimental modulation of cell-cell adhesion alters invasiveness and differentiation, indicating that adhesion complexes integrate external cues into cell-fate decisions. In yeast, flocculation protein structure and cell-cell adhesion mechanisms provide a tractable model for how adhesion complexes are regulated at the cell surface.
Turnover and disassembly
In simple terms: Adhesion complexes can be taken apart when cells need to move or divide.
Adhesion complexes are dynamic and can be disassembled or remodelled during processes such as invasion and differentiation [3,6,7]. Loss of E-cadherin cell-cell adhesion complex function is associated with lung cancer invasion and metastasis, illustrating that disassembly can have pathological consequences. Experimental modulation of adhesion in trophoblast cells similarly affects invasiveness and differentiation, confirming that turnover is functionally important.
Key Genes Involved in GO:0098635 protein complex involved in cell-cell adhesion
The following genes and proteins are representative components or regulators of protein complexes involved in cell-cell adhesion, drawn from the verified literature used in this article.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDH1 (E-cadherin) | Core transmembrane adhesion receptor in epithelial cell-cell adhesion complexes | Central to lung cancer invasion, metastasis and prognosis studies |
| CTNNB1 (beta-catenin) | Cytoplasmic plaque protein linking cadherins to actin and signalling | Key component of the E-cadherin cell-cell adhesion complex |
| ARMC8 | Evolutionarily conserved armadillo protein in cell-cell adhesion complexes | Multiple molecular interactions; model for adhesion complex assembly |
| NF2 (Merlin) | Adhesion-regulated tumour suppressor that interacts with the PAF complex | Links cell-cell adhesion to transcriptional regulation |
| C1QL3 | Promotes cell-cell adhesion by bridging ADGRB3/BAI3 and neuronal pentraxins | Neuronal adhesion complex formation |
| ADGRB3 (BAI3) | Adhesion G protein-coupled receptor in neuronal adhesion complexes | Partner of C1QL3 in cell-cell adhesion |
| Neuronal pentraxins | Secreted bridging proteins in neuronal adhesion complexes | Mediate C1QL3-dependent cell-cell adhesion |
| Actin cytoskeleton components | Provide mechanical coupling for adhesion complexes | Central to actin dynamics and cell-cell adhesion in epithelia |
| Sponge histocompatibility proteins | Ancient cell adhesion and histocompatibility factors | Evolutionary model for cell-cell adhesion |
| Yeast flocculation proteins | Surface proteins mediating cell-cell adhesion in Saccharomyces cerevisiae | Model for adhesion complex structure and mechanism |
| Trophoblast adhesion proteins | Mediate adhesion, invasion and differentiation in trophoblast cells | Experimental modulation of adhesion and invasiveness |
| PAF complex components | Transcriptional regulatory complex interacting with Merlin/NF2 | Adhesion-dependent regulation of transcription |
| Cadherin-catenin complex subunits | Assemble the core epithelial adhesion machine | Targets for cancer invasion and metastasis research |
| Armadillo-repeat proteins | Scaffold and interaction modules in adhesion complexes | Conserved across evolution; studied via Armc8 |
| Adhesion-linked signalling proteins | Transmit signals from adhesion complexes | Crosstalk with growth and differentiation pathways [5,7] |
| Neuronal adhesion complex components | Organise synaptic and neuronal adhesion | Relevant to neurobiology and synapse studies |
| Epithelial junction proteins | Maintain tissue architecture and barrier function | Studied through actin dynamics and adhesion [3,6] |
How Is protein complex involved in cell-cell adhesion Regulated?
Cell-cell adhesion complexes are regulated at multiple levels. Actin dynamics continuously remodel the adhesion machinery in epithelia, so regulators of actin polymerisation and turnover directly influence complex stability. Adhesion status can also regulate signalling complexes: cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex, providing a direct link between adhesion and transcriptional regulation. In trophoblast cells, experimental modulation of cell-cell adhesion changes invasiveness and differentiation, indicating that adhesion complexes are responsive to differentiation cues. In yeast, flocculation protein structure and cell-cell adhesion mechanisms are regulated at the cell surface, offering a genetically tractable system for studying adhesion regulation. Together these findings show that adhesion complexes are not static structures but are tuned by cytoskeletal, signalling and differentiation inputs [3,4,5,7].
protein complex involved in cell-cell adhesion and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CDH1 (E-cadherin) | Lung cancer invasion, metastasis and prognosis | Knockout or point-mutation epithelial cancer cell lines |
| NF2 (Merlin) | Adhesion-linked tumour suppressor signalling via PAF complex | Knockout and tagged knock-in models to track PAF interaction |
| C1QL3 | Neuronal adhesion and synapse-related biology | Knockout and overexpression neuronal models |
| ARMC8 | Conserved adhesion complex assembly | Knockout and knock-in models in adhesion-competent cells |
| Trophoblast adhesion proteins | Trophoblast invasion and differentiation | Experimental modulation of adhesion in trophoblast cells |
Cancer invasion and metastasis
The E-cadherin cell-cell adhesion complex is a key determinant of lung cancer invasion, metastasis and prognosis, and loss of its function is associated with more invasive tumour behaviour. Because GO:0098635 covers the protein complexes that execute cell-cell adhesion, perturbations of these complexes are directly relevant to understanding how epithelial cancers acquire invasive capacity [3,6]. Experimental modulation of adhesion in trophoblast cells further shows that changing adhesion complex activity can alter invasiveness, supporting the general principle that adhesion complexes control invasive programmes.
Neuronal adhesion and synapse biology
Neuronal adhesion complexes are specialised cell-cell adhesion machines. C1QL3 promotes cell-cell adhesion by mediating complex formation between ADGRB3/BAI3 and neuronal pentraxins, defining a neuronal adhesion complex relevant to synapse organisation. Because GO:0098635 groups protein complexes involved in cell-cell adhesion, it provides a framework for annotating and studying these neuronal assemblies alongside classical epithelial junctions.
Trophoblast differentiation and reproductive biology
In trophoblast cells, experimental modulation of cell-cell adhesion alters invasiveness and differentiation, linking adhesion complexes to placental development and differentiation programmes. This makes adhesion complex components candidate regulators of trophoblast behaviour and provides a disease-relevant context for GO:0098635.
Adhesion-linked tumour suppressor signalling
Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex, connecting adhesion complexes to a tumour suppressor pathway and to transcriptional regulation. This illustrates how adhesion complexes annotated under GO:0098635 can influence disease-relevant signalling beyond mechanical adhesion.
From protein complex involved in cell-cell adhesion-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is a candidate gene required for cell-cell adhesion complex function? | CRISPR knockout in an adhesion-competent cell line [2,6] |
| Does a specific residue control adhesion complex assembly? | CRISPR point mutation at the candidate residue [2,5] |
| Can a tagged component be tracked in live adhesion complexes? | Tagged knock-in of the endogenous gene [2,5] |
| Does increased dosage of a component strengthen or disrupt adhesion? | CRISPR overexpression model |
| Which proteins co-assemble with a known adhesion component? | Knockout plus proteomics or interaction studies [2,5] |
| How does adhesion status affect downstream signalling? | Knockout or point-mutation models combined with signalling assays [5,7] |
How to Study the protein complex involved in cell-cell adhesion Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell fluorescence imaging | Localisation and dynamics of tagged adhesion components | Tracking adhesion complex assembly at cell-cell contacts [2,3] |
| Affinity purification plus mass spectrometry | Protein partners co-assembling with a bait component | Defining complex membership for GO:0098635 [2,5] |
| CRISPR knockout followed by adhesion assays | Requirement of a gene for cell-cell adhesion | Functional validation of candidate components [2,6] |
| CRISPR point mutation | Role of a specific residue in complex function | Mechanistic dissection of adhesion proteins [2,5] |
| Overexpression assays | Effect of increased dosage on adhesion | Testing sufficiency of a component |
| Invasion and differentiation assays | Functional consequences of adhesion modulation | Trophoblast and cancer models [6,7] |
| Signalling interaction assays | Adhesion-dependent changes in signalling complexes | Merlin/NF2 and PAF complex studies |
| Comparative evolutionary analysis | Conservation of adhesion complex components | Sponge, yeast and mammalian comparisons [1,4] |
Imaging adhesion complex assembly
Fluorescence and live-cell imaging of tagged adhesion components allow researchers to visualise where and when protein complexes involved in cell-cell adhesion assemble at cell-cell contacts [2,3]. Tagged knock-in models are particularly useful because they preserve endogenous regulation while enabling tracking of complex dynamics [2,5].
Proteomic and interaction mapping
Affinity purification and proteomic approaches can identify the protein partners that co-assemble with a given adhesion component, helping to define which complexes fall under GO:0098635 [2,5]. Because Armc8 participates in cell-cell adhesion complexes through multiple molecular interactions, interaction mapping is a direct way to discover new complex members.
Functional perturbation assays
Knockout, point-mutation and overexpression experiments test whether a candidate component is required for adhesion, invasion or differentiation [2,5,6,7]. Experimental modulation of adhesion in trophoblast cells shows how functional perturbation can be combined with invasion and differentiation readouts.
Signalling readouts downstream of adhesion
Adhesion complexes influence signalling, so assays that measure pathway activity after adhesion perturbation are important. Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex, providing a concrete example of a signalling readout that can be monitored after CRISPR perturbation.
How CRISPR Can Be Used to Study GO:0098635 protein complex involved in cell-cell adhesion
Knockout
CRISPR knockout of a candidate gene is the most direct way to test whether it is required for a protein complex involved in cell-cell adhesion. Knocking out components such as CDH1 or ARMC8 can reveal loss of adhesion complex integrity and downstream phenotypes [2,6]. Knockout models are also useful for defining which proteins are essential versus redundant within a complex [2,5].
Point Mutation
CRISPR point mutation allows precise testing of residues predicted to mediate interactions within adhesion complexes. This is valuable for dissecting how individual domains or binding sites contribute to complex assembly and function [2,5]. Point-mutation models preserve the rest of the protein, making them ideal for separating adhesion functions from other roles [2,5].
Knock-in
Tagged knock-in of endogenous adhesion components enables visualisation and biochemical isolation of native complexes without overexpression artefacts [2,5]. Knock-in reporters can be used to follow complex assembly, turnover and response to signalling in real time [2,5].
Overexpression
CRISPR-mediated overexpression tests whether increasing the dosage of a component is sufficient to alter cell-cell adhesion or downstream signalling. This is particularly useful for secreted or bridging factors such as C1QL3 that promote adhesion by mediating complex formation.
How EDITGENE Supports protein complex involved in cell-cell adhesion Research
Researchers studying protein complex involved in cell-cell adhesion-related genes often need to determine whether a candidate gene is causally involved in complex assembly, adhesion strength or downstream signalling. EDITGENE provides CRISPR-based cell model services that allow such causal questions to be tested in relevant cellular backgrounds.
Contact EDITGENE today to design your custom CRISPR model for protein complex involved in cell-cell adhesion research.
Frequently Asked Questions About protein complex involved in cell-cell adhesion
What is GO:0098635?
GO:0098635 is the Gene Ontology cellular component term protein complex involved in cell-cell adhesion, defined as any protein complex capable of carrying out some part of the process of cell-cell adhesion [1,2,3].
What genes are involved in protein complex involved in cell-cell adhesion?
Representative genes include CDH1 (E-cadherin), CTNNB1, ARMC8, NF2, C1QL3, ADGRB3 and neuronal pentraxins, all of which have been linked to cell-cell adhesion complexes in published studies [2,5,6,8].
What does protein complex involved in cell-cell adhesion mean in simple terms?
It means a group of proteins that work together to stick one cell to another and to signal when that contact is made [1,3,6].
Why is GO:0098635 important in cancer?
The E-cadherin cell-cell adhesion complex is linked to lung cancer invasion, metastasis and prognosis, so adhesion complexes are central to understanding tumour progression.
How are cell-cell adhesion complexes regulated?
They are regulated by actin dynamics, signalling crosstalk such as Merlin/NF2 interaction with the PAF complex, and differentiation cues in cells such as trophoblasts [3,5,7].
What methods are used to study protein complexes involved in cell-cell adhesion?
Common methods include live-cell imaging of tagged components, affinity purification with mass spectrometry, CRISPR perturbation and functional adhesion assays [2,3,5].
Can CRISPR be used to study GO:0098635?
Yes, CRISPR knockout, point mutation, knock-in and overexpression models are all used to test the role of individual components in cell-cell adhesion complexes [2,5,8].
Is GO:0098635 found in non-mammalian organisms?
Yes, cell adhesion and histocompatibility complexes in sponges and flocculation proteins in Saccharomyces cerevisiae are examples of adhesion complexes studied in non-mammalian systems [1,4].
What is the difference between GO:0098635 and cell-cell adhesion?
Cell-cell adhesion is the biological process, while GO:0098635 is the cellular component term for the protein complexes that carry out part of that process [1,2,3].
Which diseases are linked to cell-cell adhesion complexes?
They are linked to cancer invasion and metastasis, trophoblast differentiation and neuronal adhesion biology, among other contexts [6,7,8].
Conclusion
GO:0098635, protein complex involved in cell-cell adhesion, provides a precise cellular component framework for the multi-protein machines that execute cell-cell adhesion. From epithelial cadherin-catenin complexes to neuronal adhesion assemblies and evolutionarily ancient adhesion systems, these complexes are central to tissue architecture, signalling and disease [1,3,6,8]. CRISPR-based knockout, point-mutation, knock-in and overexpression models now make it possible to test the causal role of individual components within these complexes, connecting annotation to mechanism [2,5,8].
References
- 1. Fernàndez-Busquets X et al.. 1999. Cell adhesion and histocompatibility in sponges.. Microsc Res Tech 44(4):204-18 PMID: 10098923
- 2. Gul IS et al.. 2019. Armc8 is an evolutionarily conserved armadillo protein involved in cell-cell adhesion complexes through multiple molecular interactions.. Biosci Rep 39(8) PMID: 30482882
- 3. Vasioukhin V et al.. 2001. Actin dynamics and cell-cell adhesion in epithelia.. Curr Opin Cell Biol 13(1):76-84 PMID: 11163137
- 4. Goossens K et al.. 2010. Flocculation protein structure and cell-cell adhesion mechanism in Saccharomyces cerevisiae.. Biotechnol Lett 32(11):1571-85 PMID: 20640875
- 5. Roehrig AE et al.. 2021. Cell-cell adhesion regulates Merlin/NF2 interaction with the PAF complex.. PLoS One 16(8):e0254697 PMID: 34424918
- 6. Bremnes RM et al.. 2002. The E-cadherin cell-cell adhesion complex and lung cancer invasion, metastasis, and prognosis.. Lung Cancer 36(2):115-24 PMID: 11955645
- 7. Hohn HP et al.. 2002. Experimental modulation of cell-cell adhesion, invasiveness and differentiation in trophoblast cells.. Cells Tissues Organs 172(3):218-36 PMID: 12476050
- 8. Sticco MJ et al.. 2021. C1QL3 promotes cell-cell adhesion by mediating complex formation between ADGRB3/BAI3 and neuronal pentraxins.. FASEB J 35(1):e21194 PMID: 33337553
