GO:0140360 cyclic-GMP-AMP transmembrane transporter activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0140360 describes a molecular function that enables the transfer of cyclic-GMP-AMP (cGAMP) from one side of a membrane to the other, as defined by QuickGO.
• cGAMP is a second messenger produced by cGAS that activates STING signaling, and its transmembrane transport is critical for cell-to-cell immune signaling.
• The transporter activity is linked to STING trafficking and termination, where clathrin-associated AP-1 controls STING signaling.
• Defects in cGAMP transport and STING signaling are associated with cystic fibrosis, where the STING/TBK1/IRF3/IFN type I pathway is defective.
• Autophagy and mitophagy pathways intersect with cGAMP transport and STING degradation, influencing inflammatory and autoimmune diseases.
• Research on GO:0140360 requires knockout, knock-in, and overexpression models to dissect its role in immunity and disease.
Description
Cyclic-GMP-AMP (cGAMP) is a cyclic dinucleotide second messenger generated by the enzyme cGAS in response to cytosolic DNA. Once synthesized, cGAMP binds and activates the stimulator of interferon genes (STING), initiating a signaling cascade that leads to type I interferon production and autophagy. The transfer of cGAMP across cellular membranes is essential for its function as an immunotransmitter, allowing it to act both within the producing cell and on neighboring cells. GO:0140360, cyclic-GMP-AMP transmembrane transporter activity, is the molecular function that enables this transfer from one side of a membrane to the other. Understanding this activity is crucial for deciphering how immune signals propagate between cells and how pathogens or tumors evade cGAS-STING immunity. The importance of cGAMP transport extends beyond basic immunology. Dysregulation of STING signaling, which depends on cGAMP availability and transport, is implicated in autoinflammatory diseases, cancer, and chronic infections. For example, in cystic fibrosis, the STING/TBK1/IRF3/IFN type I pathway is defective, highlighting how impaired cGAMP transport could contribute to disease pathogenesis. Moreover, autophagy and mitophagy pathways regulate STING turnover and cGAMP-mediated signaling, linking this transporter activity to broader cellular stress responses. Researchers studying GO:0140360 need robust experimental models to manipulate and measure cGAMP transport. CRISPR-based knockout, point mutation, and knock-in strategies enable precise interrogation of the genes involved, while overexpression systems can amplify signal for biochemical assays. This article provides a comprehensive overview of the mechanism, key genes, disease relevance, and research methods for GO:0140360, optimized for both human readers and AI-driven retrieval.
cyclic-GMP-AMP transmembrane transporter activity At A Glance
| GO ID | GO:0140360 |
|---|---|
| GO term | cyclic-GMP-AMP transmembrane transporter activity |
| Ontology | molecular_function |
| Synonym | none |
| Major function | Enables the transfer of cyclic-GMP-AMP from one side of a membrane to the other |
| Definition source | QuickGO |
| Related processes | STING signaling, type I interferon response, autophagy |
| Disease relevance | Cystic fibrosis, autoimmunity, cancer |
What Is GO:0140360?
GO:0140360, cyclic-GMP-AMP transmembrane transporter activity, is a molecular function defined by QuickGO as enabling the transfer of cyclic-GMP-AMP from one side of a membrane to the other. This activity is essential for moving cGAMP across cellular membranes, facilitating its role as a signaling molecule in immune responses. The term has no synonyms in QuickGO.
Why Is cyclic-GMP-AMP transmembrane transporter activity Important in Cell Biology?
GO:0140360 is important because cGAMP transport is a critical step in the cGAS-STING immune surveillance pathway, which detects cytosolic DNA and triggers interferon responses. Without proper transmembrane transport, cGAMP cannot reach STING in target cells, impairing immune signaling and allowing pathogens or tumors to escape detection. This transporter activity also intersects with autophagy and mitophagy, which control STING degradation and inflammatory balance. Thus, understanding GO:0140360 provides insights into infectious diseases, autoimmunity, and cancer immunotherapy.
• Enables cell-to-cell transfer of cGAMP for bystander STING activation.
• Central to cGAS-STING innate immune signaling and type I interferon production.
• Linked to defective STING/TBK1/IRF3/IFN pathway in cystic fibrosis.
• Regulated by autophagy and mitophagy pathways that control STING turnover.
• Implicated in autoimmune diseases where STING signaling is dysregulated.
• Potential target for cancer immunotherapy to enhance anti-tumor immunity.
• Involved in host-pathogen interactions and immune evasion.
• Requires precise CRISPR models for functional dissection.
What Happens During cyclic-GMP-AMP transmembrane transporter activity?
cGAMP Synthesis and Release
In simple terms: cGAMP is made inside a cell and then needs to get out or into another cell to send a signal.
cGAMP is synthesized by cGAS upon binding to cytosolic DNA. This second messenger can be transferred to neighboring cells via transmembrane transporters, a process that is part of the cGAS-STING pathway. The transport activity enables cGAMP to act as an immunotransmitter, propagating immune signals.
Transmembrane Transport
In simple terms: The transporter protein moves cGAMP across the membrane like a ferry.
GO:0140360 specifically enables the transfer of cGAMP from one side of a membrane to the other. This step is essential for cGAMP to reach STING in target cells, initiating downstream signaling. The molecular identity of the transporter may involve proteins associated with STING trafficking, such as clathrin-associated AP-1, which controls STING signaling termination.
STING Activation and Signaling
In simple terms: Once cGAMP gets across, it flips a switch called STING that turns on immune genes.
After transport, cGAMP binds to STING on the endoplasmic reticulum or other membranes, triggering a conformational change that activates TBK1 and IRF3, leading to type I interferon production. This pathway is defective in cystic fibrosis, where the STING/TBK1/IRF3/IFN axis is impaired.
Termination and Autophagy
In simple terms: The signal is shut off when STING is degraded by autophagy.
STING signaling is terminated by clathrin-associated AP-1, which controls STING trafficking and degradation. Autophagy and mitophagy pathways also regulate STING turnover, linking cGAMP transport to cellular homeostasis. Defects in these processes can lead to sustained inflammation.
Key Genes Involved in GO:0140360 cyclic-GMP-AMP transmembrane transporter activity
The following genes and proteins are involved in cyclic-GMP-AMP transmembrane transporter activity and its associated signaling pathways.
| Gene | Major Role | Research Relevance |
|---|---|---|
| cGAS (MB21D1) | Synthesizes cGAMP from cytosolic DNA | Upstream regulator of cGAMP availability |
| STING (TMEM173) | Binds cGAMP and activates interferon signaling | Central to cGAMP transport and signaling |
| TBK1 | Phosphorylates IRF3 downstream of STING | Key kinase in STING pathway |
| IRF3 | Transcription factor for type I interferon | Effector of STING signaling |
| AP-1 (clathrin-associated) | Controls STING trafficking and termination | Regulates STING signaling |
| ATG5 | Autophagy machinery component | Regulates STING degradation |
| ATG7 | Autophagy machinery component | Regulates STING degradation |
| PINK1 | Mitophagy regulator | Links mitophagy to STING and inflammation |
| ATP2A2 (SERCA2) | Calcium pump regulating STING signaling | Modulates STING-driven autophagy |
| GSDMD | Pyroptosis executor | Links inflammation to cGAMP responses |
| CFTR | Chloride channel mutated in cystic fibrosis | Associated with defective STING pathway |
| OPTN | Autophagy receptor | Regulates STING trafficking |
| SQSTM1 (p62) | Autophagy receptor | Regulates STING degradation |
| NLRP3 | Inflammasome sensor | Cross-talk with STING signaling |
| IL-1β | Pro-inflammatory cytokine | Downstream of inflammasome and STING |
| IFN-β | Type I interferon | Readout of STING activation |
| LC3B | Autophagosome marker | Monitors autophagy of STING |
How Is cyclic-GMP-AMP transmembrane transporter activity Regulated?
The activity of cyclic-GMP-AMP transmembrane transporter activity is regulated at multiple levels. Autophagy and mitophagy pathways control the degradation of STING, thereby limiting cGAMP-mediated signaling. Specifically, PINK1-deficiency leads to mitochondrial iron accumulation and colon tumorigenesis, linking mitophagy to STING regulation. ATP2A2 (SERCA2) regulates STING1/MITA-driven signal transduction, including selective autophagy. Additionally, clathrin-associated AP-1 controls the termination of STING signaling by regulating its trafficking. These regulatory mechanisms ensure that cGAMP transport and STING activation are tightly controlled to prevent excessive inflammation.
cyclic-GMP-AMP transmembrane transporter activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| STING (TMEM173) | Cystic fibrosis, autoimmunity | Knockout and knock-in cell lines |
| PINK1 | Colon tumorigenesis, mitophagy | PINK1 knockout models |
| ATP2A2 | STING-driven autophagy | Overexpression and point mutation |
| CFTR | Cystic fibrosis | CFTR mutant knock-in |
| ATG5 | Inflammatory bowel disease | ATG5 knockout |
Cystic Fibrosis
In cystic fibrosis, the STING/TBK1/IRF3/IFN type I pathway is defective, which may impair cGAMP-mediated immune responses. This defect could contribute to chronic infections and inflammation characteristic of the disease.
Autoimmune and Autoinflammatory Diseases
Dysregulated STING signaling, dependent on cGAMP transport, is implicated in autoimmune diseases such as systemic lupus erythematosus and Aicardi-Goutières syndrome. Mitophagy defects can exacerbate inflammation by failing to clear STING.
Cancer
cGAMP transport and STING activation are critical for anti-tumor immunity. PINK1-deficiency facilitates mitochondrial iron accumulation and colon tumorigenesis, suggesting a link between mitophagy, STING, and cancer. Enhancing cGAMP transport could improve immunotherapy outcomes.
Inflammatory Bowel Disease
Autophagy and gut microbiota interactions influence inflammatory responses in IBD, and cGAMP transport may modulate intestinal epithelial barrier function through STING signaling.
From cyclic-GMP-AMP transmembrane transporter activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate cGAMP transport? | Knockout cell line |
| Does a point mutation in STING affect cGAMP binding? | Point mutation knock-in |
| Can overexpression of transporter enhance cGAMP uptake? | Overexpression stable line |
| Where is the transporter localized? | Tagged knock-in (e.g., GFP) |
| What is the role of autophagy in cGAMP transport? | ATG5/ATG7 knockout |
| How does PINK1 deficiency affect STING signaling? | PINK1 knockout |
How to Study the cyclic-GMP-AMP transmembrane transporter activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screen | Gene essentiality for cGAMP transport | Discovery of novel transporters |
| Transport assay | Direct cGAMP flux across membranes | Functional validation of GO:0140360 |
| Live-cell imaging | Localization and trafficking of STING | Visualizing cGAMP transport |
| RNA-seq | Transcriptional changes | Interferon signature analysis |
| Proteomics | Protein interactions and modifications | Identifying STING complex components |
| Autophagy flux assay | LC3 lipidation and STING degradation | Linking autophagy to cGAMP transport |
| Mitophagy assay | Mitochondrial clearance | Role of PINK1 in STING regulation |
| Cytokine ELISA | IFN-β and IL-1β secretion | Readout of STING activation |
CRISPR Knockout Screening
Genome-wide CRISPR knockout screens can identify genes required for cGAMP transmembrane transport and STING signaling. This approach is powerful for discovering novel transporters and regulators.
Biochemical Transport Assays
Using radiolabeled or fluorescently labeled cGAMP, transport activity can be measured in membrane vesicles or intact cells. These assays directly quantify GO:0140360 activity.
Imaging and Trafficking Studies
Live-cell imaging of tagged STING and cGAMP analogs can reveal the spatiotemporal dynamics of cGAMP transport and STING activation.
Transcriptomics and Proteomics
RNA-seq and proteomics can profile gene expression changes upon cGAMP stimulation or transporter manipulation, identifying downstream pathways.
How CRISPR Can Be Used to Study GO:0140360 cyclic-GMP-AMP transmembrane transporter activity
Knockout
CRISPR knockout of candidate genes such as STING, cGAS, or autophagy regulators can abolish cGAMP transport and signaling, providing causal evidence for their role in GO:0140360.
Point Mutation
Introducing point mutations in STING or transporter genes can dissect specific residues required for cGAMP binding or translocation, as seen in studies of STING trafficking.
Knock-in
Knock-in of tagged versions of STING or transporters enables visualization and biochemical purification of the transport machinery.
Overexpression
Overexpression of cGAMP transporters or STING can amplify signaling for biochemical assays and drug screening.
How EDITGENE Supports cyclic-GMP-AMP transmembrane transporter activity Research
Researchers studying cyclic-GMP-AMP transmembrane transporter activity-related genes often need to determine whether a candidate gene is causally involved in cGAMP transport, STING signaling, or immune regulation. EDITGENE provides a comprehensive suite of CRISPR services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for cyclic-GMP-AMP transmembrane transporter activity research.
Frequently Asked Questions About cyclic-GMP-AMP transmembrane transporter activity
What is cyclic-GMP-AMP transmembrane transporter activity?
It is a molecular function (GO:0140360) that enables the transfer of cyclic-GMP-AMP from one side of a membrane to the other, as defined by QuickGO.
What genes are involved in cyclic-GMP-AMP transmembrane transporter activity?
Key genes include cGAS, STING, TBK1, IRF3, and autophagy-related genes such as ATG5 and PINK1.
How is cGAMP transported across membranes?
The transport is mediated by specific transporter proteins that facilitate the movement of cGAMP, though the exact molecular identity is still under investigation.
What diseases are associated with cGAMP transport?
Cystic fibrosis, autoimmune diseases, inflammatory bowel disease, and cancer have been linked to defects in cGAMP transport and STING signaling.
How can I study GO:0140360 in the lab?
You can use CRISPR knockout, knock-in, overexpression models, transport assays, and imaging techniques.
What is the role of STING in cGAMP transport?
STING is the downstream receptor for cGAMP; its trafficking and activation are tightly linked to cGAMP transport.
Does autophagy regulate cGAMP transport?
Yes, autophagy and mitophagy control STING degradation and thus modulate cGAMP-mediated signaling.
What are the research methods for cGAMP transport?
Methods include CRISPR screens, biochemical transport assays, live-cell imaging, RNA-seq, and proteomics.
Why is cGAMP transport important for immunity?
It allows cGAMP to act as an immunotransmitter, activating STING in neighboring cells and amplifying interferon responses.
Can EDITGENE help with CRISPR models for cGAMP transport?
Yes, EDITGENE provides knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services for studying GO:0140360.
Conclusion
GO:0140360, cyclic-GMP-AMP transmembrane transporter activity, is a critical molecular function in the cGAS-STING immune pathway. Its role in transferring cGAMP across membranes enables cell-to-cell immune signaling and is tightly regulated by autophagy and trafficking machinery. Dysregulation of this activity is linked to cystic fibrosis, autoimmunity, and cancer, making it a promising target for therapeutic intervention. Researchers can leverage CRISPR-based models and advanced screening methods to dissect the genes and mechanisms underlying cGAMP transport. EDITGENE offers comprehensive services to support these efforts, from knockout and knock-in cell lines to bioinformatics analysis, accelerating discoveries in this dynamic field.
References
- 1. Burdette BE et al.. 2021. Gasdermin D in pyroptosis.. Acta Pharm Sin B 11(9):2768-2782 PMID: 34589396
- 2. Larabi A et al.. 2020. New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD.. Autophagy 16(1):38-51 PMID: 31286804
- 3. Foerster EG et al.. 2022. How autophagy controls the intestinal epithelial barrier.. Autophagy 18(1):86-103 PMID: 33906557
- 4. Xu Y et al.. 2020. Emerging views of mitophagy in immunity and autoimmune diseases.. Autophagy 16(1):3-17 PMID: 30951392
- 5. Liu Y et al.. 2022. Clathrin-associated AP-1 controls termination of STING signalling.. Nature 610(7933):761-767 PMID: 36261523
- 6. Arcos M et al.. 2025. PINK1-deficiency facilitates mitochondrial iron accumulation and colon tumorigenesis.. Autophagy 21(4):737-753 PMID: 39512202
- 7. Yang X et al.. 2025. ATP2A2 regulates STING1/MITA-driven signal transduction including selective autophagy.. Autophagy 21(10):2230-2245 PMID: 40265346
- 8. Occhigrossi L et al.. 2023. The STING/TBK1/IRF3/IFN type I pathway is defective in cystic fibrosis.. Front Immunol 14:1093212 PMID: 36923406
