GO:0031106 septin ring organization: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031106 septin ring organization describes the control of formation, spatial distribution, and breakdown of the septin ring, a conserved cytoskeletal structure at the cell division site.
• Septin ring assembly requires cycles of GTP loading and hydrolysis by Cdc42p, linking polarity signaling to cytoskeletal organization.
• The septin ring transitions into a collar during cytokinesis, and this dynamic reorganization is essential for cell division.
• Septin filaments are compacted into rings by the anillin Mid2 and contractile ring constriction, revealing mechanical control of ring architecture.
• Nim1-related kinases regulate septin organization and cytokinesis by modulating Hof1 at the division site.
• In fungal pathogens such as Magnaporthe oryzae, the MoLfa1 protein regulates septin ring formation and fungal development.
Description
Septin ring organization (GO:0031106) is a biological process that controls the formation, spatial distribution, and breakdown of the septin ring, a filamentous cytoskeletal structure that forms at the site of cell division in fungi and animals. Septins are GTP-binding proteins that assemble into higher-order structures, and their organization into a ring at the bud neck or cleavage furrow is critical for cytokinesis, cell polarity, and membrane remodeling. The septin ring is not a static structure; it undergoes dynamic transitions, including assembly, compaction, and disassembly, which are tightly coupled to the cell cycle and to the actomyosin contractile ring. In budding yeast, septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p, and the ring later splits into a double ring or collar that persists through cytokinesis. In animal cells, a septin double ring controls the spatiotemporal organization of the ESCRT machinery during cytokinetic abscission, highlighting an evolutionarily conserved role in membrane fission. Because septin ring organization is essential for cell division and is implicated in fungal pathogenesis and human disease, researchers study it using genetics, live-cell imaging, and biochemical approaches.
septin ring organization At A Glance
| GO ID | GO:0031106 |
|---|---|
| GO term | septin ring organization |
| Ontology | biological_process |
| Synonym | septin ring organisation |
| Definition | Control of the formation, spatial distribution, and breakdown of the septin ring. |
| Major function | Assembly, positioning, and disassembly of the septin ring at the cell division site. |
| Cellular context | Bud neck in fungi; cleavage furrow in animal cells. |
| Key regulators | Cdc42p, anillin Mid2, Hof1, Nim1-related kinases. |
| Related processes | Cytokinesis, cell polarity, membrane abscission. |
What Is GO:0031106?
According to the Gene Ontology, GO:0031106 septin ring organization is defined as the control of the formation, spatial distribution, and breakdown of the septin ring. This process encompasses the molecular events that assemble septin monomers and complexes into a ring structure at specific cellular locations, maintain its position and architecture over time, and eventually disassemble it. The septin ring is a conserved cytoskeletal element that forms at the cell division site in fungi and at the cleavage furrow in animal cells, and its organization is dynamically regulated during the cell cycle.
Why Is septin ring organization Important in Cell Biology?
Septin ring organization is fundamental to cell division and morphogenesis across eukaryotes. In budding yeast, the septin ring acts as a scaffold that recruits and organizes the actomyosin contractile ring and other cytokinesis factors, and its dynamic rearrangement into a collar is required for proper cell separation. In animal cells, a septin double ring controls the spatiotemporal organization of the ESCRT machinery during cytokinetic abscission, a process essential for the final separation of daughter cells. Disruption of septin ring organization leads to cytokinesis defects, abnormal cell morphology, and multinucleation, and in fungal pathogens it impairs development and virulence. Thus, understanding GO:0031106 provides mechanistic insight into fundamental cell biology and identifies potential targets for antifungal and anticancer strategies.
• Essential for cytokinesis and cell division in fungi and animals.
• Controls the spatial organization of the ESCRT machinery during abscission.
• Regulates cell polarity and cell shape in yeast.
• Required for fungal development and pathogenesis in Magnaporthe oryzae.
• Involves GTP loading and hydrolysis by Cdc42p, linking signaling to cytoskeletal dynamics.
• Modulated by Nim1-related kinases and Hof1 at the division site.
• Requires anillin Mid2 for filament compaction into rings.
• Dysregulation is associated with cytokinesis failure and disease.
• Provides a model for studying cytoskeletal ring assembly and disassembly.
• Offers targets for antifungal and anticancer therapeutic development.
What Happens During septin ring organization?
Initiation and GTP-dependent assembly
In simple terms: The septin ring starts to form when septin proteins are switched on by a small signaling molecule called Cdc42p.
Septin ring assembly begins with the recruitment of septin complexes to the future division site, a process that requires cycles of GTP loading and hydrolysis by Cdc42p. In budding yeast, Cdc42p acts as a master regulator of polarity and directly influences septin ring formation, and perturbations in GTP cycling lead to defective ring assembly. This step establishes the initial ring structure and sets the stage for subsequent maturation and compaction.
Ring compaction and collar formation
In simple terms: After the ring forms, it tightens and then splits into a collar-like structure that stays at the division site.
Following initial assembly, septin filaments are compacted into a tight ring, a process that requires the anillin Mid2 and contractile ring constriction. Live-cell imaging in Saccharomyces cerevisiae has revealed that the septin ring transitions into a collar, which persists at the bud neck during cytokinesis. This dynamic reorganization is coupled to the cell cycle and to the actomyosin ring, ensuring proper spatial coordination of division events.
Regulation by kinases and Hof1
In simple terms: Specific enzymes called kinases add chemical tags to proteins, controlling when and where the septin ring is organized.
Nim1-related kinases regulate septin organization and cytokinesis by modulating Hof1 at the cell division site. Hof1 is a conserved F-BAR protein that interacts with the septin ring and the contractile ring, and its phosphorylation status affects the timing of septin ring dynamics. This regulatory layer ensures that septin ring organization is coordinated with other cytokinetic events.
Disassembly and breakdown
In simple terms: Once cell division is complete, the septin ring is taken apart so the cell can start a new cycle.
The final stage of septin ring organization is its breakdown, which involves disassembly of septin filaments and removal of ring components from the division site. In budding yeast, the septin collar is disassembled after cytokinesis, and this step is required for cell separation and for the next round of budding. Defects in disassembly can lead to persistent septin structures and cytokinesis defects.
Key Genes Involved in GO:0031106 septin ring organization
The following genes and proteins are central to septin ring organization, as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDC42 | GTPase that cycles between GTP-loaded and GDP-loaded states to drive septin ring assembly | Key regulator of polarity and septin ring initiation; target for studying GTP-dependent assembly |
| SEPT2 | Core septin component that polymerizes into filaments and rings | Human septin; involved in ESCRT organization during abscission |
| SEPT6 | Septin family member contributing to ring architecture | Studied in cytokinesis and membrane remodeling |
| SEPT9 | Septin filament component; forms part of the double ring | Implicated in abscission and cell division |
| MID2 | Anillin-like protein required for septin filament compaction into rings | Links contractile ring constriction to septin ring organization |
| HOF1 | F-BAR protein modulated by Nim1-related kinases to regulate septin organization | Connects kinase signaling to septin ring dynamics |
| NIM1 | Nim1-related kinase that regulates septin organization and cytokinesis | Potential target for modulating septin ring assembly |
| MO LFA1 | Protein regulating fungal development and septin ring formation in Magnaporthe oryzae | Virulence factor; model for fungal septin biology |
| CDC3 | Budding yeast septin involved in ring formation | Model septin for live-cell imaging of ring dynamics |
| CDC10 | Budding yeast septin component of the ring and collar | Used to study septin collar formation |
| CDC11 | Septin required for ring assembly and stability | Genetic model for septin ring organization |
| CDC12 | Essential septin for ring formation in yeast | Classic marker for septin ring studies |
| GIN4 | Kinase involved in septin ring assembly and stability | Regulates septin phosphorylation and ring dynamics |
| CLA4 | PAK kinase that phosphorylates septins and affects ring organization | Links signaling to septin ring assembly |
| ELM1 | Kinase that regulates septin ring formation and cell polarity | Genetic modifier of septin organization |
| ESCRT-III | Complex organized by septin double ring during abscission | Downstream effector of septin ring function |
How Is septin ring organization Regulated?
Septin ring organization is regulated by multiple signaling pathways and post-translational modifications. In budding yeast, the small GTPase Cdc42p controls septin ring assembly through cycles of GTP loading and hydrolysis, and perturbation of this cycle disrupts ring formation. Nim1-related kinases modulate Hof1 at the division site to regulate septin organization and cytokinesis. Additionally, kinases such as Gin4, Cla4, and Elm1 phosphorylate septins and influence ring assembly and stability. The anillin Mid2 and contractile ring constriction provide mechanical regulation of septin filament compaction into rings. These regulatory inputs ensure that septin ring organization is temporally and spatially coupled to the cell cycle and to actomyosin ring dynamics.
septin ring organization and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SEPT9 | Cytokinesis failure and cancer | Knockout in HeLa cells followed by live-cell imaging |
| SEPT2 | Abscission defects and genomic instability | Point mutation of GTP-binding domain |
| MoLFA1 | Fungal pathogenesis in Magnaporthe oryzae | Knockout in fungal strain and infection assay |
| MID2 | Cytokinesis defects and septin ring compaction failure | Knockout in budding yeast and fluorescence microscopy |
| HOF1 | Impaired septin organization and cytokinesis | Point mutation of phosphorylation sites |
Septin ring organization in fungal pathogenesis
In the rice blast fungus Magnaporthe oryzae, the MoLfa1 protein regulates fungal development and septin ring formation, and disruption of this process impairs pathogenicity. Septin ring organization is therefore a potential antifungal target, as proper septin function is required for appressorium formation and host infection.
Septin ring organization and cytokinesis failure in cancer
Defects in septin ring organization can lead to cytokinesis failure, resulting in multinucleation and genomic instability, which are hallmarks of cancer. The septin double ring controls ESCRT-mediated abscission, and its dysfunction may contribute to aneuploidy and tumor progression. Thus, components of GO:0031106 are of interest as cancer biomarkers and therapeutic targets.
Septin ring organization in neurodegenerative and developmental disorders
Septins are highly expressed in the nervous system, and mutations in septin genes have been linked to neurodegenerative diseases and developmental disorders. Although direct evidence for GO:0031106 in these conditions is still emerging, the conserved role of septin ring organization in cell division and membrane dynamics suggests that its dysregulation could contribute to disease pathology.
From septin ring organization-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a septin gene disrupt ring formation? | Knockout cell line (e.g., SEPT9 KO) |
| How does a specific mutation affect GTP cycling? | Point mutation knock-in of CDC42 |
| Where does a tagged septin localize during division? | Tagged knock-in (e.g., GFP-SEPT2) |
| Does overexpression of a regulator alter ring dynamics? | Overexpression of MID2 or HOF1 |
| Which genes are required for septin ring assembly? | CRISPR library screening in yeast or human cells |
| How does a fungal pathogen require septin ring organization? | Knockout of MoLFA1 in Magnaporthe oryzae |
How to Study the septin ring organization Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Dynamics of septin ring assembly and disassembly | Visualizing ring formation in yeast or human cells |
| CRISPR knockout | Loss-of-function effects on septin ring organization | Identifying essential genes for ring assembly |
| Point mutation knock-in | Effect of specific amino acid changes on ring function | Studying GTP cycling in Cdc42p |
| Co-immunoprecipitation | Protein interactions within the septin ring | Mapping the septin interactome |
| Phosphoproteomics | Phosphorylation sites on septins and regulators | Identifying kinase targets |
| Fungal infection assay | Virulence linked to septin ring formation | Testing antifungal targets |
| RNA-seq | Transcriptional changes upon septin perturbation | Pathway analysis of septin-related genes |
| Proximity labeling | Spatial proteome of the septin ring | Identifying ESCRT components at the division site |
Live-cell fluorescence microscopy
Live-cell imaging of fluorescently tagged septins (e.g., GFP-Cdc10 or GFP-SEPT2) allows real-time visualization of ring assembly, compaction, and disassembly. This method is essential for defining the stages of septin ring organization and for quantifying dynamic parameters such as ring intensity and diameter.
Genetic perturbation and phenotypic analysis
Knockout or point mutation of septin genes and their regulators (e.g., CDC42, MID2, HOF1) followed by phenotypic assays reveals their roles in septin ring organization and cytokinesis. In fungal pathogens, gene deletion and infection assays link septin ring formation to virulence.
Biochemical and proteomic approaches
Co-immunoprecipitation and mass spectrometry can identify protein-protein interactions within the septin ring and its regulators. Phosphoproteomics can map post-translational modifications on septins and associated proteins, revealing regulatory inputs.
CRISPR-based screening
Genome-wide CRISPR knockout or activation screens can identify genes that regulate septin ring organization and cytokinesis. Such screens are powerful for discovering novel components and for linking GO:0031106 to disease-relevant pathways.
How CRISPR Can Be Used to Study GO:0031106 septin ring organization
Knockout
CRISPR knockout of septin genes such as SEPT9 or regulators like CDC42 can abolish septin ring formation, leading to cytokinesis defects and multinucleation. These models are used to study the requirement for specific genes in GO:0031106 and to assess downstream effects on cell proliferation.
Point Mutation
Point mutation knock-in of GTP-binding residues in CDC42 or phosphorylation sites in HOF1 allows precise dissection of regulatory mechanisms without completely removing the protein. Such models reveal how specific residues control septin ring assembly and disassembly.
Knock-in
Tagged knock-in of septin genes (e.g., GFP-SEPT2 or mCherry-CDC10) enables live-cell imaging of ring dynamics at endogenous expression levels. This approach is ideal for tracking the spatiotemporal organization of the septin ring in real time.
Overexpression
Overexpression of septin regulators such as MID2 or HOF1 can alter septin ring compaction and stability, providing gain-of-function models to study the consequences of dysregulated ring organization. These models are useful for testing whether increased levels of a regulator are sufficient to drive ring formation or disassembly.
How EDITGENE Supports septin ring organization Research
Researchers studying septin ring organization-related genes often need to determine whether a candidate gene is causally involved in ring assembly, positioning, or disassembly. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell models, enabling functional validation of genes implicated in GO:0031106 and its associated diseases.
Contact EDITGENE today to design your custom CRISPR model for septin ring organization research.
Frequently Asked Questions About septin ring organization
What is septin ring organization?
Septin ring organization (GO:0031106) is the biological process that controls the formation, spatial distribution, and breakdown of the septin ring, a cytoskeletal structure essential for cell division.
What genes are involved in septin ring organization?
Key genes include CDC42, SEPT2, SEPT6, SEPT9, MID2, HOF1, and Nim1-related kinases, as well as fungal-specific regulators like MoLFA1.
Where does septin ring organization occur?
It occurs at the bud neck in budding yeast and at the cleavage furrow in animal cells, where the septin ring coordinates cytokinesis and abscission.
Why is septin ring organization important for cell division?
It provides a scaffold for the contractile ring and ESCRT machinery, ensuring proper membrane abscission and daughter cell separation.
How is septin ring organization regulated?
It is regulated by Cdc42p GTP cycling, Nim1-related kinases, Hof1, and anillin Mid2, as well as by phosphorylation events.
What happens when septin ring organization is disrupted?
Disruption leads to cytokinesis failure, multinucleation, abnormal cell morphology, and in fungal pathogens, reduced virulence.
What methods are used to study septin ring organization?
Live-cell imaging, CRISPR knockout, point mutation knock-in, co-immunoprecipitation, and proteomics are commonly used.
Is septin ring organization conserved across species?
Yes, septin ring organization is conserved from fungi to animals, with core components and regulatory mechanisms shared.
Can septin ring organization be targeted for antifungal therapy?
Yes, because septin ring formation is essential for fungal development and pathogenesis, it is a potential antifungal target.
How can CRISPR help study septin ring organization?
CRISPR enables knockout, point mutation, knock-in, and overexpression models to dissect gene function in septin ring organization.
Conclusion
Septin ring organization (GO:0031106) is a conserved and dynamic process that controls the assembly, positioning, and disassembly of the septin ring at the cell division site. It is essential for cytokinesis, membrane abscission, and cell polarity, and its dysregulation is linked to cytokinesis failure and fungal pathogenesis. Understanding the molecular mechanisms and regulatory inputs of septin ring organization provides insights into fundamental cell biology and offers opportunities for therapeutic intervention. EDITGENE's CRISPR services empower researchers to generate precise models for studying this process and its role in disease.
References
- 1. Karasmanis EP et al.. 2019. A Septin Double Ring Controls the Spatiotemporal Organization of the ESCRT Machinery in Cytokinetic Abscission.. Curr Biol 29(13):2174-2182.e7 PMID: 31204162
- 2. Varela Salgado M et al.. 2024. Septin Organization and Dynamics for Budding Yeast Cytokinesis.. J Fungi (Basel) 10(9) PMID: 39330402
- 3. Wu JQ et al.. 2024. The MoLfa1 Protein Regulates Fungal Development and Septin Ring Formation in Magnaporthe oryzae.. Int J Mol Sci 25(6) PMID: 38542408
- 4. Chen H et al.. 2011. Dynamics of septin ring and collar formation in Saccharomyces cerevisiae.. Biol Chem 392(8-9):689-97 PMID: 21736496
- 5. Arbizzani F et al.. 2022. Septin filament compaction into rings requires the anillin Mid2 and contractile ring constriction.. Cell Rep 39(3):110722 PMID: 35443188
- 6. Bhojappa B et al.. 2026. Nim1-related kinases regulate septin organization and cytokinesis by modulating Hof1 at the cell division site.. Elife 14 PMID: 42713960
- 7. Gladfelter AS et al.. 2005. Interplay between septin organization, cell cycle and cell shape in yeast.. J Cell Sci 118(Pt 8):1617-28 PMID: 15784684
- 8. Gladfelter AS et al.. 2002. Septin ring assembly involves cycles of GTP loading and hydrolysis by Cdc42p.. J Cell Biol 156(2):315-26 PMID: 11807094
