GO:0031105 septin complex: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031105 (septin complex) is a cellular component defined as a protein complex containing septins, typically oligomeric and composed of multiple septin subunits.
• Septins are GTP-binding cytoskeletal proteins that assemble into hetero-oligomeric complexes and higher-order filaments, functioning in cytokinesis, polarity, and membrane compartmentalization.
• The mammalian septin interactome includes dozens of proteins, linking septin complexes to actin, microtubules, and signaling pathways.
• Septin complexes are essential for epithelial cell polarity by connecting the catenin complex to the actin cytoskeleton.
• Septins regulate RhoA activation and exocyst recruitment to the cilium transition zone, highlighting roles in ciliogenesis and cell signaling.
• Dysregulation of septin complexes is implicated in cancer, neurodegeneration, and autoimmune encephalitis, making them attractive therapeutic targets.
Description
The septin complex (GO:0031105) is a cellular component defined as a protein complex containing septins, which are GTP-binding proteins that assemble into oligomeric structures. Septins were first identified in yeast as cell division cycle mutants and have since been recognized as a conserved fourth component of the cytoskeleton, alongside actin, microtubules, and intermediate filaments. These complexes are critical for diverse cellular processes, including cytokinesis, cell polarity, membrane dynamics, and vesicle trafficking. In mammalian cells, septin complexes are composed of multiple septin subunits that form hetero-oligomeric rods and filaments, often associating with actin and microtubule networks. The functional importance of septin complexes is underscored by their involvement in human diseases, such as cancer, neurodegenerative disorders, and autoimmune encephalitis. Understanding the composition, assembly, and regulation of septin complexes is therefore essential for researchers in cell biology, developmental biology, and disease pathology.
septin complex At A Glance
| GO ID | GO:0031105 |
|---|---|
| GO term | septin complex |
| Ontology | cellular_component |
| Synonym | none |
| Major function | Forms oligomeric structures involved in cytokinesis, cell polarity, and membrane compartmentalization |
| Composition | Hetero-oligomeric complexes of multiple septin subunits |
| Associated processes | Cytokinesis, epithelial polarity, ciliogenesis, vesicle trafficking |
| Disease relevance | Cancer, neurodegeneration, autoimmune encephalitis |
What Is GO:0031105?
GO:0031105 (septin complex) refers to a protein complex that contains septins, which are a family of GTP-binding proteins. These complexes are typically oligomeric, meaning they consist of multiple septin subunits assembled together, and they serve as structural and functional units in various cellular contexts.
Why Is septin complex Important in Cell Biology?
Septin complexes are fundamental to cellular organization and function, acting as scaffolds that recruit signaling proteins and coordinate cytoskeletal dynamics. Their role in cytokinesis is essential for cell division, and their involvement in polarity and membrane trafficking affects tissue architecture and cell migration. Dysregulation of septin complexes has been linked to various human diseases, including cancer and neurological disorders, making them important targets for research and therapeutic development.
• Essential for cytokinesis and cell division.
• Regulates cell polarity and epithelial architecture.
• Coordinates with actin and microtubule cytoskeletons.
• Involved in ciliogenesis and transition zone recruitment.
• Plays roles in vesicle trafficking and exocytosis.
• Associated with cancer progression and metastasis.
• Implicated in neurodegenerative diseases.
• Linked to autoimmune encephalitis.
• Target for antiviral and antibacterial strategies.
• Provides a model for studying oligomeric protein complexes.
Core Biology of septin complex
Assembly of septin complexes
In simple terms: Septin proteins come together to form larger structures.
Septins assemble into hetero-oligomeric complexes, typically containing multiple septin subunits. These complexes can further polymerize into filaments and higher-order structures. The assembly is regulated by GTP binding and interactions with other proteins.
Role in cytokinesis
In simple terms: Septin complexes help cells divide by forming a ring at the cleavage furrow.
During cytokinesis, septin complexes localize to the cleavage furrow and are required for the completion of cell division. They interact with actin and myosin to coordinate membrane ingression and abscission.
Function in cell polarity
In simple terms: Septin complexes help cells know which way is up and down.
Septin complexes link the catenin complex to the actin cytoskeleton, establishing epithelial cell polarity. This connection is crucial for maintaining tissue organization and barrier function.
Interaction with signaling pathways
In simple terms: Septin complexes talk to other proteins to control cell behavior.
Septins interact with RhoA and the exocyst complex to recruit the cilium transition zone, influencing ciliogenesis and cell signaling. They also participate in the mammalian septin interactome, which includes numerous proteins involved in diverse pathways.
Regulation by sumoylation
In simple terms: Septin complexes can be modified by adding small tags that change their behavior.
Transient sumoylation of septins regulates the recruitment of Fir1-Skt5 complex between split septin rings, affecting septin dynamics and function.
Key Genes Involved in GO:0031105 septin complex
The following genes encode septin proteins and related factors that are key components or regulators of the septin complex.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SEPT2 | Core septin subunit | Forms hetero-oligomers; implicated in cancer and neurodegeneration |
| SEPT3 | Core septin subunit | Involved in neuronal development and synaptic function |
| SEPT4 | Core septin subunit | Linked to Parkinson's disease and cancer |
| SEPT5 | Core septin subunit | Associated with leukemia and platelet function |
| SEPT6 | Core septin subunit | Mutated in leukemia; role in cytokinesis |
| SEPT7 | Core septin subunit | Essential for cytokinesis; tumor suppressor candidate |
| SEPT8 | Core septin subunit | Involved in membrane trafficking |
| SEPT9 | Core septin subunit | Biomarker for colorectal cancer |
| SEPT10 | Core septin subunit | Expressed in testis; role in spermatogenesis |
| SEPT11 | Core septin subunit | Regulates ciliogenesis and cell polarity |
| SEPT12 | Core septin subunit | Mutated in male infertility |
| SEPT14 | Core septin subunit | Expressed in brain; role in neuronal function |
| RhoA | Signaling GTPase | Activates exocyst to recruit transition zone |
| Fir1 | Septin-associated protein | Regulated by sumoylation; involved in septin ring dynamics |
| Skt5 | Septin-associated protein | Part of Fir1-Skt5 complex |
| Catenin complex | Cell adhesion | Links septins to actin cytoskeleton for polarity |
| Exocyst complex | Vesicle trafficking | Recruited by septins for ciliogenesis |
How Is septin complex Regulated?
Septin complex assembly and function are regulated by GTP binding, post-translational modifications such as sumoylation, and interactions with regulatory proteins like Fir1 and Skt5. Additionally, septin dynamics are influenced by the actin and microtubule cytoskeletons and by signaling pathways involving RhoA.
septin complex and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SEPT9 | Colorectal cancer | Knockout in HCT116 cells; overexpression in normal colon cells |
| SEPT4 | Parkinson's disease | Knockout in dopaminergic neurons; point mutation models |
| SEPT5 | Leukemia | Knockout in hematopoietic stem cells; knock-in of mutations |
| SEPT12 | Male infertility | Knockout in mouse models; knock-in of patient mutations |
| SEPT7 | Cancer and cytokinesis defects | Knockout in HeLa cells; rescue with tagged knock-in |
Septin complexes in cancer
Alterations in septin expression and function have been observed in various cancers. For example, SEPT9 is a biomarker for colorectal cancer, and other septins are implicated in tumorigenesis and metastasis.
Septin complexes in neurodegeneration
Septin complexes are important for neuronal function, and their dysfunction has been linked to neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease.
Septin complexes in autoimmune encephalitis
Autoantibodies against septin complexes have been identified in patients with autoimmune encephalitis, highlighting their role as autoantigens in neurological disorders.
From septin complex-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of SEPT9 in cytokinesis? | SEPT9 knockout HeLa cells |
| How do septin mutations affect neuronal function? | Knock-in of SEPT4 mutations in iPSC-derived neurons |
| What is the interactome of septin complexes? | Tagged knock-in of SEPT2 in HEK293T cells followed by mass spectrometry |
| How does sumoylation regulate septin dynamics? | Point mutation of sumoylation sites in SEPT7 |
| Does overexpression of SEPT11 affect ciliogenesis? | Overexpression of SEPT11 in RPE1 cells |
| Can septin complexes be targeted in cancer? | Knockout of SEPT9 in colorectal cancer organoids |
How to Study the septin complex Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Affinity purification-mass spectrometry | Protein interactions | Identifying septin complex components |
| Live-cell imaging | Dynamic localization | Visualizing septin ring formation |
| CRISPR knockout screens | Gene essentiality | Finding modifiers of septin function |
| In vitro polymerization assays | Filament assembly | Studying septin biochemistry |
| Immunofluorescence | Subcellular localization | Detecting septin complexes in tissues |
| FRAP | Protein dynamics | Measuring septin turnover |
| Proximity ligation assay | Protein-protein interactions | Detecting septin interactions in situ |
Proteomic analysis of septin complexes
Affinity purification coupled with mass spectrometry can identify septin complex components and interacting proteins. Tagged knock-in of septin subunits allows for endogenous complex isolation.
Imaging septin dynamics
Fluorescence microscopy of GFP-tagged septins enables visualization of complex assembly and dynamics in live cells. Super-resolution microscopy can reveal filament structures.
Genetic screens for septin function
CRISPR knockout screens can identify genes that interact with septins or are required for septin complex function. RNAi screens have also been used.
Biochemical assays for septin assembly
In vitro reconstitution with purified septin proteins can test GTP binding, polymerization, and interactions with other proteins.
How CRISPR Can Be Used to Study GO:0031105 septin complex
Knockout
CRISPR knockout of septin genes can reveal their essential roles in cytokinesis, polarity, and development. For example, SEPT9 knockout in cancer cell lines reduces proliferation and induces cytokinesis defects.
Point Mutation
Introducing point mutations in septin genes can mimic disease-associated variants or disrupt GTP binding. This helps dissect the molecular mechanisms of septin function.
Knock-in
Knock-in of tagged septins (e.g., GFP or HA) allows for endogenous expression and purification of septin complexes for interactome studies.
Overexpression
Overexpression of septins can lead to aberrant filament formation and disrupt cellular processes, providing insights into their dosage-sensitive roles.
How EDITGENE Supports septin complex Research
Researchers studying septin complex-related genes often need to determine whether a candidate gene is causally involved in cellular processes or disease. EDITGENE provides comprehensive CRISPR services to enable such investigations.
Contact EDITGENE today to design your custom CRISPR model for septin complex research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SEPTIN7 Knockout HEK293 Cell Line | EDJ-KQ3540 | Human | 989 | Details Get a Quote |
| SEPTIN1 Knockout HEK293 Cell Line | EDJ-KQ4444 | Human | 1731 | Details Get a Quote |
| SEPTIN2 Knockout HEK293 Cell Line | EDJ-KQ5327 | Human | 4735 | Details Get a Quote |
| SEPTIN5 Knockout HEK293 Cell Line | EDJ-KQ5500 | Human | 5413 | Details Get a Quote |
| SEPTIN4 Knockout HEK293 Cell Line | EDJ-KQ5501 | Human | 5414 | Details Get a Quote |
| SEPTIN9 Knockout HEK293 Cell Line | EDJ-KQ6541 | Human | 10801 | Details Get a Quote |
| SEPTIN6 Knockout HEK293 Cell Line | EDJ-KQ7858 | Human | 23157 | Details Get a Quote |
| SEPTIN8 Knockout HEK293 Cell Line | EDJ-KQ7865 | Human | 23176 | Details Get a Quote |
| SEPTIN12 Knockout HEK293 Cell Line | EDJ-KQ8540 | Human | 124404 | Details Get a Quote |
| SEPTIN10 Knockout HEK293 Cell Line | EDJ-KQ11317 | Human | 151011 | Details Get a Quote |
| SEPTIN3 Knockout HEK293 Cell Line | EDJ-KQ15225 | Human | 55964 | Details Get a Quote |
| SEPTIN11 Knockout HEK293 Cell Line | EDJ-KQ15226 | Human | 55752 | Details Get a Quote |
| SEPTIN14 Knockout HEK293 Cell Line | EDJ-KQ15227 | Human | 346288 | Details Get a Quote |
| SEPTIN9 Knockout A-549 Cell Line | EDJ-KQ32095 | Human | 10801 | Details Get a Quote |
| SEPTIN9 Knockout HCT 116 Cell Line | EDJ-KQ32096 | Human | 10801 | Details Get a Quote |
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Frequently Asked Questions About septin complex
What is the septin complex?
The septin complex (GO:0031105) is a protein complex containing septins, typically oligomeric, involved in cytokinesis, cell polarity, and membrane dynamics.
What genes are involved in the septin complex?
Genes encoding septins such as SEPT2, SEPT3, SEPT4, SEPT5, SEPT6, SEPT7, SEPT8, SEPT9, SEPT10, SEPT11, SEPT12, and SEPT14, as well as associated proteins like RhoA and Fir1.
What is the function of septin complexes?
They function in cytokinesis, cell polarity, membrane compartmentalization, vesicle trafficking, and ciliogenesis.
How are septin complexes assembled?
Septins assemble into hetero-oligomeric complexes in a GTP-dependent manner, forming filaments and higher-order structures.
What diseases are associated with septin complexes?
Cancer, neurodegenerative diseases, and autoimmune encephalitis.
How can I study septin complexes in the lab?
Using CRISPR knockout, knock-in, overexpression, imaging, proteomics, and biochemical assays.
What is the role of septins in cell division?
Septins form a ring at the cleavage furrow during cytokinesis and are required for cell division.
Are septins involved in cell polarity?
Yes, septin complexes link the catenin complex to the actin cytoskeleton to establish epithelial polarity.
What is the relationship between septins and cilia?
Septins regulate RhoA activation and exocyst recruitment to the cilium transition zone, affecting ciliogenesis.
How does sumoylation affect septin complexes?
Sumoylation of septins regulates the recruitment of Fir1-Skt5 complex and septin ring dynamics.
Conclusion
The septin complex (GO:0031105) is a vital cellular component with diverse roles in cytokinesis, polarity, and membrane dynamics. Its dysfunction is linked to cancer, neurodegeneration, and autoimmune diseases. Continued research using advanced CRISPR models and proteomic approaches will further elucidate its mechanisms and therapeutic potential.
References
- 1. Cao L et al.. 2009. The evolution, complex structures and function of septin proteins.. Cell Mol Life Sci 66(20):3309-23 PMID: 19597764
- 2. Wang X et al.. 2021. The septin complex links the catenin complex to the actin cytoskeleton for establishing epithelial cell polarity.. J Mol Cell Biol 13(6):395-408 PMID: 34143183
- 3. Safavian D et al.. 2023. Septin-mediated RhoA activation engages the exocyst complex to recruit the cilium transition zone.. J Cell Biol 222(4) PMID: 36912772
- 4. Schampera JN et al.. 2024. Septin dynamics and organization in mammalian cells.. Curr Opin Cell Biol 91:102442 PMID: 39509956
- 5. Estey MP et al.. 2011. Septins.. Curr Biol 21(10):R384-7 PMID: 21601794
- 6. Müller J et al.. 2024. Transient septin sumoylation steers a Fir1-Skt5 protein complex between the split septin ring.. J Cell Biol 223(1) PMID: 37938157
- 7. Neubauer K et al.. 2017. The Mammalian Septin Interactome.. Front Cell Dev Biol 5:3 PMID: 28224124
- 8. Kalbitz S et al.. 2024. Anti-septin complex positive autoimmune encephalitis after severe falciparum malaria: a case report.. Malar J 23(1):369 PMID: 39663534
