GO:0036213 contractile ring contraction: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0036213 contractile ring contraction is the biological process by which an actomyosin ring decreases in diameter, a key step in cytokinesis.
• The contractile ring is composed of actin filaments, myosin II motors, and associated proteins that generate tension and drive constriction.
• Two mechanisms contribute to ring tension: sliding filament (myosin sliding actin) and fixed filament (actin crosslinking and bundling).
• Curvature-induced expulsion of actomyosin bundles is a recently described phenomenon that helps explain ring contraction dynamics.
• Defects in contractile ring contraction are linked to cytokinesis failure, which can lead to aneuploidy and cancer.
• Research on contractile ring contraction uses advanced imaging, genetic perturbation, and biophysical modeling to dissect molecular mechanisms.
Description
Contractile ring contraction (GO:0036213) is a fundamental biological process that drives cytokinesis, the physical separation of a cell into two daughter cells. This process involves the constriction of a dynamic actomyosin ring, which generates the force needed to pinch the cell membrane inward. Understanding how this ring contracts is critical for deciphering the mechanisms of cell division, tissue homeostasis, and developmental processes. Researchers study contractile ring contraction to uncover the molecular machinery and biophysical principles underlying cell division. Defects in this process can result in cytokinesis failure, leading to genomic instability and diseases such as cancer. Recent studies have highlighted the role of actin filament sliding and crosslinking in generating ring tension, as well as the importance of curvature-induced bundle expulsion during contraction. This article provides a comprehensive overview of GO:0036213, integrating authoritative QuickGO data with real PubMed literature to describe its definition, mechanisms, key genes, regulation, disease relevance, and research methodologies.
contractile ring contraction At A Glance
| GO ID | GO:0036213 |
|---|---|
| GO term | contractile ring contraction |
| Ontology | biological_process |
| Synonym | contractile ring constriction |
| Major function | Constriction of actomyosin ring during cytokinesis |
| Definition | The process of an actomyosin ring getting smaller in diameter. |
| Related cellular component | Contractile ring (actomyosin ring) |
| Related molecular functions | Actin filament binding, motor activity, crosslinking |
| Key processes | Cytokinesis, cell division, actomyosin ring assembly and constriction |
What Is GO:0036213?
According to the Gene Ontology, contractile ring contraction (GO:0036213) is defined as the process of an actomyosin ring getting smaller in diameter. This process is synonymous with contractile ring constriction and is a critical step in cytokinesis, where the ring constricts to divide the cytoplasm.
Why Is contractile ring contraction Important in Cell Biology?
Contractile ring contraction is essential for cytokinesis, ensuring proper cell division and genomic stability. Dysregulation of this process can lead to cytokinesis failure, resulting in binucleation, aneuploidy, and tumorigenesis. Moreover, understanding the biophysical mechanisms of ring contraction provides insights into fundamental cell biology and potential therapeutic targets for diseases characterized by aberrant cell division.
• Essential for cytokinesis and cell division.
• Prevents aneuploidy and genomic instability.
• Implicated in cancer development when defective.
• Involved in developmental processes and tissue morphogenesis.
• Provides a model for studying actomyosin mechanics.
• Target for understanding cytokinesis-related diseases.
• Key to deciphering biophysical principles of cell shape changes.
• Relevant to regenerative medicine and stem cell division.
What Happens During contractile ring contraction?
Initiation of Ring Assembly
In simple terms: The cell sets up a ring made of actin and myosin just under the membrane.
Contractile ring contraction begins with the assembly of an actomyosin ring at the equatorial cortex of the dividing cell. This ring is composed of actin filaments, myosin II motors, and accessory proteins that crosslink and bundle actin. The assembly is spatially and temporally regulated to ensure proper positioning and function.
Activation of Myosin Motors
In simple terms: Myosin motors start pulling on actin filaments to generate force.
Myosin II motors are activated by phosphorylation, enabling them to bind actin filaments and generate contractile force through ATP hydrolysis. This activation is crucial for the onset of ring contraction.
Sliding Filament Mechanism
In simple terms: Myosin slides actin filaments past each other, shortening the ring.
In the sliding filament mechanism, myosin II motors move along actin filaments, causing them to slide relative to one another, which reduces the ring diameter. This process requires continuous ATP hydrolysis and is a major contributor to ring tension.
Fixed Filament Mechanism
In simple terms: Actin filaments are crosslinked and bundled, providing structural support for contraction.
The fixed filament mechanism involves actin crosslinking proteins that stabilize actin bundles, allowing the ring to maintain tension without continuous sliding. This mechanism complements sliding filament activity to ensure efficient contraction.
Curvature-Induced Bundle Expulsion
In simple terms: As the ring bends, some actin bundles are pushed out, helping the ring shrink.
Recent studies have shown that during contraction, actomyosin bundles can be expelled from the ring due to curvature-induced forces. This expulsion contributes to the reduction in ring diameter and may facilitate the final stages of constriction.
Completion of Constriction
In simple terms: The ring closes completely, pinching the cell into two.
The final step of contractile ring contraction involves the complete closure of the ring, leading to abscission and separation of daughter cells. This step is tightly regulated and coordinated with membrane remodeling and other cytokinetic events.
Key Genes Involved in GO:0036213 contractile ring contraction
The following genes and proteins are key players in contractile ring contraction, as identified in the provided literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ACTB | Actin filament component | Forms the structural backbone of the contractile ring |
| MYH9 | Myosin II motor | Generates force for ring contraction |
| MYH10 | Myosin II motor | Non-muscle myosin involved in cytokinesis |
| RHOa | Regulator of actomyosin | Controls ring assembly and contraction |
| ROCK1 | Rho kinase | Phosphorylates myosin light chain to activate myosin |
| ROCK2 | Rho kinase | Regulates actomyosin dynamics |
| ANLN | Actin binding protein | Essential for contractile ring assembly |
| SEPT9 | Septin filament | Scaffolds ring components |
| EZR | ERM protein | Links actin to membrane |
| MSN | Moesin | Crosslinks actin and membrane |
| RDX | Radixin | Actin-membrane linker |
| PFN1 | Profilin | Regulates actin polymerization |
| COF1 | Cofilin | Actin depolymerization |
| ARPC2 | Arp2/3 complex | Nucleates actin branches |
| WASL | WASP-like | Activates Arp2/3 |
| FMNL1 | Formin | Elongates actin filaments |
| DIAPH1 | Formin | Actin nucleation and elongation |
How Is contractile ring contraction Regulated?
Contractile ring contraction is regulated by multiple signaling pathways, including the RhoA-ROCK pathway, which controls myosin light chain phosphorylation and actin dynamics. Additionally, calcium signaling and mechanical feedback mechanisms fine-tune the contraction process.
contractile ring contraction and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| RHOa | Cancer, cytokinesis failure | Knockout cell lines, xenograft models |
| MYH9 | Aneuploidy, tumorigenesis | Point mutation knock-in mice |
| ANLN | Cancer, cytokinesis defects | Overexpression cell models |
| ROCK1 | Cancer, metastasis | CRISPR knockout organoids |
| SEPT9 | Developmental disorders | Knock-in reporter cell lines |
Cancer and Genomic Instability
Defects in contractile ring contraction can lead to cytokinesis failure, resulting in binucleation and aneuploidy, which are hallmarks of cancer. Dysregulation of key regulators such as RhoA and myosin II has been implicated in tumorigenesis.
Developmental Disorders
Proper contractile ring contraction is essential for embryonic development and tissue morphogenesis. Mutations in genes involved in this process can cause developmental abnormalities.
Neurodegeneration
Emerging evidence suggests that cytokinesis defects may contribute to neurodegenerative diseases, although the link to contractile ring contraction specifically requires further investigation.
From contractile ring contraction-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate contractile ring contraction? | CRISPR knockout cell line |
| How does a specific mutation affect ring dynamics? | Point mutation knock-in |
| Where does protein X localize during contraction? | Tagged knock-in (e.g., GFP) |
| Does overexpression of gene Y alter contraction? | Overexpression cell model |
| What is the role of gene Z in cytokinesis? | Conditional knockout mouse |
| Can a drug target contractile ring contraction? | High-throughput screening with CRISPR libraries |
How to Study the contractile ring contraction Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Ring dynamics and protein localization | Visualizing contraction in real-time |
| CRISPR knockout | Gene function | Identifying essential genes |
| FRET biosensors | Myosin activation | Monitoring signaling during contraction |
| Optical tweezers | Ring tension | Quantifying mechanical forces |
| Proteomics | Protein composition | Identifying ring-associated proteins |
| RNAi knockdown | Gene knockdown effects | Phenotypic analysis |
| High-content screening | Phenotypic changes | Drug discovery |
Live-Cell Imaging
Live-cell imaging using fluorescently tagged actin and myosin allows real-time visualization of contractile ring contraction dynamics. This method provides spatiotemporal information on ring assembly and constriction.
Genetic Perturbation
CRISPR/Cas9 knockout, knockdown, or overexpression of candidate genes enables functional analysis of their roles in contractile ring contraction. This approach can reveal essential components and regulators.
Biophysical Measurements
Force measurements using optical tweezers or micropipette aspiration can quantify tension generated by the contractile ring. These techniques help elucidate the mechanical properties of the ring.
Proteomics and Interactomics
Mass spectrometry-based proteomics can identify proteins associated with the contractile ring and their post-translational modifications. This provides insights into the molecular composition and regulation.
How CRISPR Can Be Used to Study GO:0036213 contractile ring contraction
Knockout
CRISPR knockout of genes such as MYH9 or RHOa can abolish contractile ring contraction, leading to cytokinesis failure. This approach is used to study gene essentiality.
Point Mutation
Introducing point mutations in genes like MYH9 can mimic human disease variants and reveal their impact on ring contraction. This helps in understanding structure-function relationships.
Knock-in
Knock-in of fluorescent tags (e.g., GFP) into endogenous loci allows visualization of protein dynamics during contraction. This is valuable for live-cell imaging.
Overexpression
Overexpression of genes such as ANLN can perturb ring contraction and provide insights into dosage effects. This model is useful for gain-of-function studies.
How EDITGENE Supports contractile ring contraction Research
Researchers studying contractile ring contraction-related genes often need to determine whether a candidate gene is causally involved in the process or is merely correlated with it. EDITGENE provides a comprehensive suite of CRISPR services to enable precise genetic perturbations and functional studies.
Contact EDITGENE today to design your custom CRISPR model for contractile ring contraction research.
Frequently Asked Questions About contractile ring contraction
What is contractile ring contraction?
Contractile ring contraction (GO:0036213) is the process by which an actomyosin ring decreases in diameter during cytokinesis.
What genes are involved in contractile ring contraction?
Key genes include ACTB, MYH9, RHOa, ROCK1, ANLN, and SEPT9, among others.
How does the contractile ring generate force?
Force is generated by myosin II motors sliding actin filaments and by actin crosslinking that maintains tension.
What is the role of RhoA in contractile ring contraction?
RhoA activates ROCK, which phosphorylates myosin light chain to promote myosin activity and ring contraction.
What happens if contractile ring contraction fails?
Failure can lead to cytokinesis defects, binucleation, aneuploidy, and cancer.
How can I study contractile ring contraction in the lab?
Use live-cell imaging, CRISPR knockouts, and biophysical measurements to analyze ring dynamics.
What is the sliding filament mechanism?
It is the process where myosin motors slide actin filaments past each other to reduce ring diameter.
What is curvature-induced bundle expulsion?
It is the phenomenon where actomyosin bundles are expelled from the ring due to curvature, aiding contraction.
Which diseases are linked to contractile ring contraction defects?
Cancer and developmental disorders are associated with defects in this process.
Can CRISPR be used to study contractile ring contraction?
Yes, CRISPR knockout, knock-in, and overexpression models are powerful tools for functional studies.
Conclusion
Contractile ring contraction (GO:0036213) is a critical biological process that ensures proper cell division. Understanding its molecular mechanisms, regulation, and disease relevance is essential for advancing cell biology and medicine. EDITGENE provides comprehensive CRISPR solutions to facilitate research in this field.
References
- 2. Huang J et al.. 2016. Curvature-induced expulsion of actomyosin bundles during cytokinetic ring contraction.. Elife 5 PMID: 27734801
- 4. Alonso-Matilla R et al.. 2019. Sliding filament and fixed filament mechanisms contribute to ring tension in the cytokinetic contractile ring.. Cytoskeleton (Hoboken) 76(11-12):611-625 PMID: 31443136
