GO:0032185 septin cytoskeleton organization: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0032185 septin cytoskeleton organization describes the assembly, arrangement, and disassembly of septin-based cytoskeletal structures.
• Septins form hetero-oligomeric complexes that assemble into filaments, rings, and gauzes at the plasma membrane and other cellular sites.
• Septin dynamics are regulated by phosphorylation, GTP binding, and interactions with other cytoskeletal elements.
• Disrupted septin organization is linked to male infertility, ocular hypertension, and neuronal diseases.
• Key septin genes include SEPT1 through SEPT12, with specific roles in cell division, membrane compartmentalization, and vesicle trafficking.
• CRISPR-based knockout, knock-in, and overexpression models are essential for dissecting septin function in health and disease.
Description
Septins are a conserved family of GTP-binding proteins that assemble into higher-order cytoskeletal structures, including filaments, rings, and gauzes. The process by which these structures are assembled, arranged, and disassembled is formally annotated as septin cytoskeleton organization (GO:0032185). This biological process is critical for diverse cellular functions, such as cytokinesis, cell polarity, membrane compartmentalization, and vesicle trafficking. Researchers study septin cytoskeleton organization to understand fundamental cell biology and its implications in human diseases, including cancer, neurodegeneration, and infertility. The dynamic nature of septin structures requires precise regulation by phosphorylation, GTP hydrolysis, and interactions with actin and microtubules. Advances in imaging and CRISPR-based genetic tools have accelerated the dissection of septin assembly pathways and their physiological roles.
septin cytoskeleton organization At A Glance
| GO ID | GO:0032185 |
|---|---|
| GO term | septin cytoskeleton organization |
| Ontology | biological_process |
| Synonym | septin cytoskeleton organisation; septin cytoskeleton organization and biogenesis |
| Major function | Assembly, arrangement, and disassembly of septin-based cytoskeletal structures |
| Cellular location | Plasma membrane, cleavage furrow, cell cortex, and other subcellular sites |
| Key regulators | Phosphorylation, GTP binding, septin-interacting proteins |
| Associated diseases | Male infertility, ocular hypertension, neurodegenerative disorders |
What Is GO:0032185?
Septin cytoskeleton organization (GO:0032185) is the cellular process that results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures composed of septin complexes and their associated proteins. This includes the formation of septin filaments, rings, and higher-order assemblies at specific subcellular locations, as well as their remodeling in response to cellular signals.
Why Is septin cytoskeleton organization Important in Cell Biology?
Septin cytoskeleton organization is fundamental to cell shape, division, and membrane dynamics, and its dysregulation is increasingly recognized in human pathologies ranging from infertility to glaucoma and cancer. Understanding this process provides insights into basic cell biology and offers potential therapeutic targets.
• Essential for cytokinesis and cell division.
• Maintains structural integrity of spermatozoa and male fertility.
• Regulates membrane compartmentalization and vesicle trafficking.
• Involved in neuronal development and function.
• Dysregulated in ocular hypertension and glaucoma.
• Plays a role in host-pathogen interactions and bacterial toxin effects.
• Provides a model for studying cytoskeletal dynamics and self-assembly.
• Potential target for cancer and neurodegenerative disease therapies.
• Requires precise phosphoregulation, linking signaling pathways to cytoskeletal remodeling.
• Offers opportunities for CRISPR-based functional genomics.
What Happens During septin cytoskeleton organization?
Septin Complex Assembly
In simple terms: Septin proteins pair up to form building blocks that can assemble into larger structures.
Septins form hetero-oligomeric complexes, typically hexamers or octamers, through interactions between different septin subunits. These complexes are the basic building blocks for higher-order structures. The assembly is guided by GTP binding and specific protein-protein interactions.
Filament and Ring Formation
In simple terms: The building blocks link together to form long threads or rings inside cells.
Septin complexes polymerize end-to-end to form filaments, which can further organize into rings, bundles, or gauzes at the plasma membrane. These structures are dynamic and can rearrange during processes like cell division.
Membrane Association and Compartmentalization
In simple terms: Septin structures attach to membranes and help create separate zones within cells.
Septin filaments associate with the plasma membrane via lipid interactions and specific binding proteins, forming diffusion barriers that compartmentalize membrane domains. This is crucial for polarized cell functions and vesicle trafficking.
Disassembly and Remodeling
In simple terms: Septin structures can be taken apart and rebuilt when cells need to change shape or divide.
Septin cytoskeleton organization includes disassembly, which is regulated by phosphorylation and other post-translational modifications. Remodeling allows rapid responses to cellular signals during cytokinesis, cell migration, and differentiation.
Key Genes Involved in GO:0032185 septin cytoskeleton organization
The following genes encode septin proteins and related regulators that are central to septin cytoskeleton organization.
| Gene | Major Role | Research Relevance |
|---|---|---|
| SEPT1 | Septin filament component | Cell division, membrane dynamics |
| SEPT2 | Core septin complex subunit | Cytokinesis, neurodegeneration |
| SEPT3 | Neuronal septin | Synaptic function, Alzheimer's disease |
| SEPT4 | Sperm annulus component | Male infertility, spermatogenesis |
| SEPT5 | Platelet septin | Platelet function, leukemia |
| SEPT6 | Septin complex subunit | Cell cycle regulation |
| SEPT7 | Central septin filament organizer | Cytokinesis, cancer |
| SEPT8 | Septin complex subunit | Membrane trafficking |
| SEPT9 | Septin ring component | Cancer biomarker, cell polarity |
| SEPT10 | Septin complex subunit | Ciliogenesis |
| SEPT11 | Septin filament regulator | DNA repair, cancer |
| SEPT12 | Sperm midpiece septin | Male infertility |
| SEPT14 | Septin family member | Spermatogenesis |
| CDC42 | Regulator of septin assembly | Cytoskeletal dynamics |
| ANLN | Septin-interacting protein | Cytokinesis |
| BORG | Septin-associated protein | Cell polarity |
| GTP | Cofactor for septin assembly | Structural integrity |
How Is septin cytoskeleton organization Regulated?
Septin cytoskeleton organization is regulated by phosphorylation, particularly by kinases such as Aurora B and Cdk1, which control septin dynamics during mitosis. GTP binding and hydrolysis by septins themselves are also critical for assembly and disassembly. Additionally, interactions with actin and microtubule cytoskeletons and with regulatory proteins like Borg and anillin modulate septin organization.
septin cytoskeleton organization and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| SEPT4 | Male infertility | Knockout mouse, sperm analysis |
| SEPT12 | Male infertility | Point mutation knock-in |
| SEPT9 | Cancer biomarker | Overexpression in cancer cell lines |
| SEPT2 | Neurodegeneration | Neuronal knockout |
| SEPT7 | Cytokinesis defects | CRISPR knockout in HeLa cells |
Male Infertility
Disruption of septin cytoskeleton organization in spermatozoa leads to structural defects and impaired motility, contributing to male infertility. SEPT4 and SEPT12 mutations are associated with abnormal sperm annulus and midpiece formation.
Ocular Hypertension and Glaucoma
Dysregulation of septin cytoskeletal organization in the trabecular meshwork contributes to increased intraocular pressure and ocular hypertension, a major risk factor for glaucoma.
Neurodegenerative Diseases
Septin dysfunction and altered phosphorylation have been implicated in neuronal development disorders and neurodegenerative diseases such as Alzheimer's and Parkinson's.
Cancer
Altered expression and organization of septins are observed in various cancers, affecting cell division, invasion, and metastasis.
From septin cytoskeleton organization-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| What is the role of SEPT7 in cytokinesis? | SEPT7 knockout cell line |
| How do SEPT4 mutations affect sperm structure? | SEPT4 point mutation knock-in mouse |
| Does SEPT9 overexpression promote cancer? | SEPT9 overexpression in cancer cells |
| Where does SEPT2 localize during mitosis? | Tagged knock-in of SEPT2 |
| How does phosphorylation regulate septin assembly? | Phospho-mutant knock-in |
| What genes interact with septins? | CRISPR library screening |
How to Study the septin cytoskeleton organization Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Fluorescence microscopy | Septin localization and dynamics | Visualizing ring formation |
| Super-resolution imaging | Nanoscale septin architecture | Filament ultrastructure |
| Mass spectrometry | Protein interactions | Identifying septin complex partners |
| CRISPR knockout screens | Gene function in septin organization | Discovering regulators |
| GTPase assays | GTP binding/hydrolysis | Septin activity |
| Phosphoproteomics | Phosphorylation sites | Regulation of septin dynamics |
| Live-cell imaging | Real-time septin remodeling | Cytokinesis studies |
Fluorescence Microscopy
Live-cell and fixed-cell fluorescence microscopy, including super-resolution techniques, visualize septin filament and ring dynamics in real time.
Proteomics and Interactomics
Mass spectrometry-based proteomics identifies septin complex components and interacting proteins, revealing assembly pathways.
CRISPR Genetic Screens
Genome-wide CRISPR knockout or activation screens uncover genes that regulate septin cytoskeleton organization.
Biochemical Assays
GTP binding, hydrolysis, and polymerization assays characterize septin biochemical properties and regulation.
How CRISPR Can Be Used to Study GO:0032185 septin cytoskeleton organization
Knockout
CRISPR knockout of septin genes (e.g., SEPT7, SEPT9) disrupts septin complex formation, leading to cytokinesis defects and altered cell morphology, enabling functional studies.
Point Mutation
Introducing disease-associated point mutations (e.g., in SEPT4 or SEPT12) via CRISPR knock-in recapitulates human phenotypes in cell and animal models.
Knock-in
Tagged knock-in of septin genes (e.g., GFP-SEPT2) allows real-time visualization of septin dynamics and localization in live cells.
Overexpression
CRISPR activation or cDNA overexpression of septins (e.g., SEPT9) models gain-of-function effects observed in cancers and other diseases.
How EDITGENE Supports septin cytoskeleton organization Research
Researchers studying septin cytoskeleton organization-related genes often need to determine whether a candidate gene is causally involved in assembly, disassembly, or disease phenotypes. EDITGENE provides comprehensive CRISPR-based services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for septin cytoskeleton organization research.
Frequently Asked Questions About septin cytoskeleton organization
What is septin cytoskeleton organization?
Septin cytoskeleton organization (GO:0032185) is the cellular process that assembles, arranges, and disassembles cytoskeletal structures made of septin complexes and associated proteins.
What genes are involved in septin cytoskeleton organization?
Key genes include SEPT1 through SEPT14, as well as regulators like CDC42 and ANLN.
How is septin cytoskeleton organization regulated?
It is regulated by phosphorylation, GTP binding, and interactions with other cytoskeletal elements.
What diseases are linked to septin cytoskeleton organization?
Diseases include male infertility, ocular hypertension, neurodegenerative disorders, and cancer.
What methods are used to study septin cytoskeleton organization?
Common methods include fluorescence microscopy, proteomics, CRISPR screens, and biochemical assays.
Can CRISPR be used to study septin cytoskeleton organization?
Yes, CRISPR knockout, knock-in, and overexpression models are widely used to dissect septin function.
What is the role of SEPT7 in septin cytoskeleton organization?
SEPT7 is a central component of septin complexes and is essential for filament formation and cytokinesis.
How does septin cytoskeleton organization affect sperm?
Proper septin organization is required for sperm structural integrity and motility; defects cause male infertility.
Is septin cytoskeleton organization involved in cancer?
Yes, altered septin expression and organization contribute to cancer progression and metastasis.
What model systems are used to study septin cytoskeleton organization?
Cell lines, mouse models, and CRISPR-engineered cells are commonly used.
Conclusion
Septin cytoskeleton organization (GO:0032185) is a vital biological process that governs the assembly and dynamics of septin-based structures, impacting cell division, membrane organization, and human health. Dysregulation of this process is linked to infertility, ocular hypertension, neurodegeneration, and cancer. Continued research using advanced CRISPR and imaging tools will further elucidate the molecular mechanisms and therapeutic potential of targeting septin cytoskeleton organization.
References
- 1. Schampera JN et al.. 2024. Septin dynamics and organization in mammalian cells.. Curr Opin Cell Biol 91:102442 PMID: 39509956
- 2. Werner B et al.. 2023. Phosphoregulation of the septin cytoskeleton in neuronal development and disease.. Cytoskeleton (Hoboken) 80(7-8):275-289 PMID: 36127729
- 3. Schwan C et al.. 2017. Formation of Nanotube-Like Protrusions, Regulation of Septin Organization and Re-guidance of Vesicle Traffic by Depolymerization of the Actin Cytoskeleton Induced by Binary Bacterial Protein Toxins.. Curr Top Microbiol Immunol 399:35-51 PMID: 27726005
- 4. Marquardt J et al.. 2019. Architecture, remodeling, and functions of the septin cytoskeleton.. Cytoskeleton (Hoboken) 76(1):7-14 PMID: 29979831
- 5. Woods BL et al.. 2021. The state of the septin cytoskeleton from assembly to function.. Curr Opin Cell Biol 68:105-112 PMID: 33188984
- 6. Dunleavy JEM et al.. 2019. The cytoskeleton in spermatogenesis.. Reproduction 157(2):R53-R72 PMID: 30576284
- 7. Ihara M et al.. 2005. Cortical organization by the septin cytoskeleton is essential for structural and mechanical integrity of mammalian spermatozoa.. Dev Cell 8(3):343-52 PMID: 15737930
- 8. Maddala R et al.. 2024. Dysregulation of septin cytoskeletal organization in the trabecular meshwork contributes to ocular hypertension.. JCI Insight 9(23) PMID: 39641270
