GO:0035757 chemokine (C-C motif) ligand 19 binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035757 (chemokine (C-C motif) ligand 19 binding) is a molecular function term describing the selective interaction of a protein with the chemokine CCL19.
• CCL19 is a homeostatic chemokine that binds primarily to CCR7 and to atypical chemokine receptors such as ACKR4, orchestrating immune cell trafficking [1, 5, 6].
• CCL19 binding to CCR7 on dendritic cells and T cells is critical for their migration to lymph nodes and for immune surveillance [3, 6].
• Dysregulated CCL19 binding contributes to inflammatory diseases, bone resorption, and cancer metastasis [1, 4, 7].
• Experimental models for studying CCL19 binding include knockout mice, point-mutant receptors, and tagged knock-in reporters [2, 5, 8].
• EDITGENE offers CRISPR knockout, point mutation, knock-in, overexpression, and library screening services to dissect CCL19 binding mechanisms.
Description
Chemokine (C-C motif) ligand 19 (CCL19) is a small secreted protein that belongs to the CC chemokine family and plays a central role in directing the migration of immune cells. The molecular function defined by GO:0035757, chemokine (C-C motif) ligand 19 binding, refers to the selective interaction between a protein and CCL19, which is essential for chemokine signaling and scavenging [1, 5]. This binding event is a prerequisite for downstream cellular responses such as chemotaxis, adhesion, and immune cell recruitment [3, 6]. Researchers study CCL19 binding to understand how immune cells navigate to lymphoid organs and how this process goes awry in disease [4, 7]. The interaction of CCL19 with its receptors, particularly CCR7 and atypical chemokine receptor 4 (ACKR4), has been characterized in multiple experimental systems, revealing both canonical signaling and scavenging functions [5, 6, 8]. Because CCL19 binding is implicated in inflammation, bone remodeling, and cancer, it represents a promising target for therapeutic intervention [1, 2, 7].
chemokine (C-C motif) ligand 19 binding At A Glance
| GO ID | GO:0035757 |
|---|---|
| GO term | chemokine (C-C motif) ligand 19 binding |
| Ontology | molecular_function |
| Synonym | CCL19 binding |
| Major function | Binding to the chemokine CCL19, mediating immune cell migration and scavenging |
| Related receptors | CCR7, ACKR4 |
| Related ligands | CCL19, CCL21, CCL20 |
| Cellular context | Extracellular space, plasma membrane |
| Disease relevance | Inflammation, bone resorption, cancer metastasis |
What Is GO:0035757?
GO:0035757, chemokine (C-C motif) ligand 19 binding, is a molecular function term that describes the binding of a protein or molecular entity to the chemokine CCL19. This binding is non-covalent and selective, enabling the interacting protein to either transduce signals (as in the case of CCR7) or sequester and scavenge CCL19 (as with ACKR4) [5, 6]. The term encompasses interactions that occur at the cell surface or in the extracellular milieu, and it is a critical step in chemokine-mediated communication [1, 3].
Why Is chemokine (C-C motif) ligand 19 binding Important in Cell Biology?
Understanding chemokine (C-C motif) ligand 19 binding is fundamental to immunology because it governs the directed migration of dendritic cells, T cells, and B cells into lymphoid organs, thereby shaping adaptive immune responses [3, 6]. Moreover, CCL19 binding is involved in pathological processes such as osteoclast migration and bone resorption, and it can be modulated by shear stress in endothelial cells, linking it to vascular inflammation [1, 4]. The interaction of CCL19 with atypical receptors like ACKR4 also highlights its role in chemokine scavenging and gradient maintenance, which is crucial for proper immune cell positioning [5, 8]. Consequently, targeting CCL19 binding has therapeutic potential in autoimmune diseases, osteoporosis, and cancer [2, 7].
• CCL19 binding to CCR7 is essential for dendritic cell and T cell homing to lymph nodes [3, 6].
• It regulates immune surveillance and adaptive immunity by maintaining chemokine gradients.
• CCL19 binding stimulates osteoclast migration and bone resorption, linking it to bone diseases.
• Shear stress modulates CCL19 expression in endothelial cells, implicating it in vascular inflammation.
• Atypical chemokine receptor ACKR4 scavenges CCL19, fine-tuning immune responses [5, 8].
• CCL19 binding is exploited by cancer cells to promote metastasis to lymph nodes.
• Antibodies targeting CCR7 can block CCL19 binding, offering therapeutic strategies.
• CCL19 binding is a potential biomarker for inflammatory and autoimmune conditions.
• Genetic models (knockout, knock-in) are vital to dissect CCL19 binding in vivo [6, 8].
• CRISPR screening can identify novel regulators of CCL19 binding.
What Happens During chemokine (C-C motif) ligand 19 binding?
CCL19 Secretion and Gradient Formation
In simple terms: Cells release CCL19, which then forms a concentration gradient to attract immune cells.
CCL19 is secreted by stromal cells in lymphoid organs and by activated endothelial cells, where its expression can be induced by shear stress. Once secreted, CCL19 binds to glycosaminoglycans on cell surfaces, creating a immobilized gradient that guides migrating cells. This gradient is essential for the directed movement of CCR7-expressing cells, such as dendritic cells and naive T cells, toward lymph nodes.
Receptor Engagement and Specificity
In simple terms: CCL19 docks onto specific receptors on the surface of target cells, like a key fitting a lock.
CCL19 binds with high affinity to CCR7, a G protein-coupled receptor, and to atypical chemokine receptor ACKR4 [5, 6]. The binding specificity is determined by the N-terminal region of CCL19 and the extracellular loops of the receptor. ACKR4 can also bind CCL19 and internalize it for scavenging, thereby shaping the gradient [5, 8]. The interaction of CCL19 with CCR7 is modulated by the receptor's oligomeric state; shifting CCR7 towards its monomeric form augments CCL19 binding and uptake.
Signal Transduction and Cellular Responses
In simple terms: Once CCL19 binds, it triggers a chain reaction inside the cell that leads to movement and other responses.
Upon binding to CCR7, CCL19 induces conformational changes that activate heterotrimeric G proteins, leading to downstream signaling cascades involving PI3K, Rac, and actin reorganization [3, 6]. This results in chemotaxis, integrin activation, and cell survival. In osteoclasts, CCL19 binding stimulates migration and bone resorption through similar signaling pathways. The binding of CCL19 to ACKR4, in contrast, does not activate G proteins but recruits GRK3 and beta-arrestins to mediate scavenging.
Scavenging and Termination of Signaling
In simple terms: Some receptors act like vacuum cleaners, removing CCL19 to stop the signal.
Atypical chemokine receptors such as ACKR4 bind CCL19 and internalize it, leading to degradation and termination of the chemokine gradient [5, 8]. This scavenging function is crucial for preventing excessive immune cell recruitment and for maintaining homeostasis. ACKR4 can recruit GRK3 prior to beta-arrestins, and it can scavenge chemokines even in the absence of beta-arrestins, highlighting a distinct regulatory mechanism. CCL20, another chemokine, also binds ACKR4, indicating shared scavenging pathways.
Key Genes Involved in GO:0035757 chemokine (C-C motif) ligand 19 binding
The following genes and proteins are directly involved in chemokine (C-C motif) ligand 19 binding, either as ligands, receptors, or regulatory molecules.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CCL19 | Ligand; binds CCR7 and ACKR4 | Central to the GO term; studied in immune cell migration [1, 3] |
| CCR7 | Primary signaling receptor for CCL19 | Mediates chemotaxis and survival; target for antibodies [3, 6] |
| ACKR4 | Atypical receptor; scavenges CCL19 | Regulates gradient and immune response [5, 8] |
| CCL21 | Related chemokine; also binds CCR7 | Shares functions with CCL19 in lymphoid organs |
| CCL20 | Ligand for ACKR4 | Competes with CCL19 for scavenging |
| GRK3 | Kinase recruited by ACKR4 | Modulates receptor internalization |
| ARRB1 | Beta-arrestin 1; involved in ACKR4 trafficking | Regulates scavenging |
| ARRB2 | Beta-arrestin 2; involved in ACKR4 trafficking | Regulates scavenging |
| PIK3CA | PI3K subunit; downstream of CCR7 | Mediates chemotaxis signaling |
| RAC1 | Small GTPase; actin reorganization | Required for cell migration |
| ACTB | Actin; cytoskeletal component | Enables cell movement |
| TNF | Pro-inflammatory cytokine; induces CCL19 | Links inflammation to CCL19 expression |
| IL1B | Cytokine; modulates CCL19 expression | Inflammatory regulation |
| CD83 | Dendritic cell marker; regulates CCL19 binding | Modulates immune responses |
| CCR7-AS1 | Long non-coding RNA; regulates CCR7 | Potential modulator of CCL19 binding |
| GNAI1 | G protein subunit; downstream of CCR7 | Signal transduction |
| GNAI2 | G protein subunit; downstream of CCR7 | Signal transduction |
| GNAI3 | G protein subunit; downstream of CCR7 | Signal transduction |
How Is chemokine (C-C motif) ligand 19 binding Regulated?
The binding of CCL19 to its receptors is regulated at multiple levels. Receptor oligomerization state influences binding affinity; shifting CCR7 towards its monomeric form augments CCL19 binding and uptake. Shear stress and inflammatory cytokines such as resistin modulate CCL19 expression in endothelial cells, thereby affecting the availability of ligand for binding. Atypical receptors like ACKR4 are regulated by GRK3 and beta-arrestins, which control their scavenging activity and thus the local concentration of CCL19. Additionally, CCL20 can compete with CCL19 for ACKR4 binding, providing another layer of regulation.
chemokine (C-C motif) ligand 19 binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CCL19 | Inflammatory bone loss | CCL19 knockout mice |
| CCR7 | Cancer metastasis | CCR7 point-mutant knock-in |
| ACKR4 | Immune dysregulation | ACKR4 knockout |
| CCL20 | Inflammatory diseases | CCL20 overexpression |
| CD83 | Periodontal disease | CD83 knockout dendritic cells |
CCL19 Binding in Inflammatory and Autoimmune Diseases
Dysregulated CCL19 binding contributes to chronic inflammation by promoting excessive recruitment of immune cells. In periodontal disease, a DNA vaccine targeting dendritic cells via CCL19 binding showed therapeutic potential. Shear stress-induced CCL19 expression in endothelial cells links hemodynamic forces to vascular inflammation. Targeting CCL19-CCR7 interactions with antagonistic antibodies could mitigate autoimmune conditions.
CCL19 Binding in Bone Resorption and Osteoporosis
CCL19 and CCL21 stimulate osteoclast migration and bone resorption, implicating CCL19 binding in osteoporosis and inflammatory bone loss. Inhibiting CCL19 binding may therefore represent a strategy to reduce pathological bone resorption.
CCL19 Binding in Cancer Metastasis
CCR7, the receptor for CCL19, is overexpressed in various cancers and mediates lymph node metastasis. CCL19 binding to CCR7 on cancer cells promotes migration and survival, facilitating metastatic spread [3, 7]. Blocking this interaction is a potential therapeutic approach.
From chemokine (C-C motif) ligand 19 binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CCL19 binding mediate osteoclast migration? | CCL19 knockout mice |
| How does CCR7 monomerization affect CCL19 binding? | CCR7 point mutations |
| What is the role of ACKR4 scavenging in vivo? | ACKR4 knockout mice |
| Can CCL19 binding be visualized in real time? | Tagged CCL19 knock-in |
| Does overexpression of CCL19 promote metastasis? | CCL19 overexpression in cancer cells |
| Which genes regulate CCL19 binding? | CRISPR library screening |
How to Study the chemokine (C-C motif) ligand 19 binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Radioligand binding | Affinity and receptor number | CCL19-CCR7 interaction |
| Surface plasmon resonance | Kinetics of binding | Antibody blocking |
| Transwell migration | Chemotaxis | Osteoclast migration |
| Confocal microscopy | Internalization and trafficking | ACKR4 scavenging |
| CRISPR screen | Genes regulating binding | Novel regulators |
| RNA-seq | Transcriptional changes | CCL19-induced signaling |
| Proteomics | Protein interactions | Receptor complexes |
| Intravital imaging | In vivo migration | Lymph node homing |
Binding Assays
Direct binding of CCL19 to receptors can be measured using radiolabeled or fluorescently labeled CCL19 in equilibrium binding assays. These assays determine affinity (Kd) and receptor density. Surface plasmon resonance (SPR) provides real-time kinetic measurements of CCL19-CCR7 interactions.
Cell Migration Assays
Chemotaxis assays, such as Transwell migration, assess the functional consequence of CCL19 binding by measuring directed cell movement [1, 6]. These assays are used to evaluate the impact of genetic modifications on CCL19-induced migration.
Imaging and Tracking
Fluorescently tagged CCL19 or receptors enable visualization of binding and internalization in live cells using confocal microscopy [5, 6]. Intravital imaging in mice can track CCL19-mediated cell migration in lymphoid organs.
Genetic Screening
CRISPR knockout libraries can be used to identify genes that regulate CCL19 binding and downstream signaling. RNA-seq and proteomics complement these screens by revealing expression changes.
How CRISPR Can Be Used to Study GO:0035757 chemokine (C-C motif) ligand 19 binding
Knockout
CRISPR knockout of CCL19, CCR7, or ACKR4 in cell lines or mice abolishes CCL19 binding and downstream functions, providing definitive evidence for their roles [1, 5]. For example, ACKR4 knockout mice show impaired CCL19 scavenging.
Point Mutation
Introducing point mutations in CCR7 or ACKR4 can dissect the specific residues required for CCL19 binding versus signaling. For instance, mutations that shift CCR7 to a monomeric form enhance CCL19 binding.
Knock-in
Knock-in of tagged CCL19 or receptors allows real-time tracking of binding and trafficking. Tagged CCL19 knock-in mice enable visualization of chemokine gradients in vivo.
Overexpression
Overexpression of CCL19 or its receptors in cell lines or transgenic mice can model pathological states such as cancer metastasis and chronic inflammation. This approach helps identify downstream effects of enhanced CCL19 binding.
How EDITGENE Supports chemokine (C-C motif) ligand 19 binding Research
Researchers studying chemokine (C-C motif) ligand 19 binding-related genes often need to determine whether a candidate gene is causally involved in immune cell migration, scavenging, or disease progression. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell and animal models, enabling rigorous functional validation of CCL19 binding mechanisms.
Contact EDITGENE today to design your custom CRISPR model for chemokine (C-C motif) ligand 19 binding research.
Frequently Asked Questions About chemokine (C-C motif) ligand 19 binding
What is chemokine (C-C motif) ligand 19 binding?
It is the molecular function defined by GO:0035757, describing the selective interaction of a protein with the chemokine CCL19, which is crucial for immune cell migration and scavenging [1, 5].
What genes are involved in chemokine (C-C motif) ligand 19 binding?
Key genes include CCL19 itself, its receptors CCR7 and ACKR4, and regulatory molecules such as GRK3 and beta-arrestins [3, 5, 6].
How does CCL19 binding affect immune cells?
CCL19 binding to CCR7 triggers chemotaxis, survival, and activation of dendritic cells and T cells, directing them to lymph nodes [3, 6].
What diseases are associated with CCL19 binding?
Dysregulated CCL19 binding is linked to inflammatory diseases, bone resorption, and cancer metastasis [1, 4, 7].
Can CCL19 binding be targeted therapeutically?
Yes, antibodies that block CCR7 or inhibitors of CCL19 binding are being explored for autoimmune diseases and cancer.
What is the role of ACKR4 in CCL19 binding?
ACKR4 is an atypical receptor that binds and scavenges CCL19, shaping chemokine gradients without activating G protein signaling [5, 8].
How is CCL19 binding regulated?
It is regulated by receptor oligomerization, shear stress, inflammatory cytokines, and scavenging receptors like ACKR4 [4, 5, 6].
What experimental models are used to study CCL19 binding?
Common models include knockout mice, point-mutant cell lines, tagged knock-in reporters, and overexpression systems [1, 4, 6, 7].
What methods measure CCL19 binding?
Radioligand binding, surface plasmon resonance, chemotaxis assays, and imaging techniques are widely used [3, 5, 6].
How can CRISPR help study CCL19 binding?
CRISPR knockout, point mutation, knock-in, and overexpression enable precise dissection of gene function in CCL19 binding pathways [1, 6, 8].
Conclusion
GO:0035757, chemokine (C-C motif) ligand 19 binding, is a pivotal molecular function that orchestrates immune cell trafficking and homeostasis. Its dysregulation contributes to a spectrum of diseases, from inflammation to cancer, making it a compelling target for therapeutic intervention [1, 3, 7]. Advances in CRISPR-based models and screening technologies continue to unravel the complexities of CCL19 binding, offering new opportunities for drug discovery [6, 8]. EDITGENE stands ready to support these efforts with tailored gene-editing solutions.
References
- 1. Lee J et al.. 2017. Stimulation of osteoclast migration and bone resorption by C-C chemokine ligands 19 and 21.. Exp Mol Med 49(7):e358 PMID: 28729639
- 3. Jang MS et al.. 2022. Development of a human antibody that exhibits antagonistic activity toward CC chemokine receptor 7.. Antib Ther 5(3):192-201 PMID: 35967907
- 4. Yu HR et al.. 2015. Shear Stress Modulates Resistin-Induced CC Chemokine Ligand 19 Expression in Human Aortic Endothelial Cells.. J Cell Physiol 230(9):2120-7 PMID: 25656506
- 5. Matti C et al.. 2020. ACKR4 Recruits GRK3 Prior to β-Arrestins but Can Scavenge Chemokines in the Absence of β-Arrestins.. Front Immunol 11:720 PMID: 32391018
- 6. Gerken OJ et al.. 2022. Shifting CCR7 towards Its Monomeric Form Augments CCL19 Binding and Uptake.. Cells 11(9) PMID: 35563750
- 7. Fan X et al.. 2024. A cleaved adhesin DNA vaccine targeting dendritic cell against Porphyromonas gingivalis-induced periodontal disease.. Mol Oral Microbiol 39(6):433-445 PMID: 38696249
- 8. Matti C et al.. 2020. CCL20 is a novel ligand for the scavenging atypical chemokine receptor 4.. J Leukoc Biol 107(6):1137-1154 PMID: 32533638
