GO:1902412 regulation of mitotic cytokinesis: Spatiotemporal Control, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1902412 regulation of mitotic cytokinesis describes any process that modulates the frequency, rate or extent of mitotic cytokinesis, the final step of cell division.
• Mitotic cytokinesis is driven by actomyosin ring contraction and membrane remodeling, and its regulation ensures genomic stability.
• Key regulators include the Dma1-mediated mitotic checkpoint, the mitotic exit network (MEN), and integrin-linked kinase (ILK).
• Dysregulation of cytokinesis is linked to cancer, developmental defects, and aneuploidy.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of cytokinesis regulators.
• High-content imaging, live-cell microscopy, and proteomics are standard methods to study regulation of mitotic cytokinesis.
Description
Regulation of mitotic cytokinesis (GO:1902412) encompasses any process that modulates the frequency, rate or extent of mitotic cytokinesis, the physical separation of daughter cells after mitosis. This regulation is essential for maintaining genomic integrity, as errors in cytokinesis can lead to binucleation, aneuploidy, and tumorigenesis. The process is highly conserved from yeast to humans, with core machinery including the actomyosin contractile ring, septins, and membrane trafficking components. In budding yeast, the mitotic exit network (MEN) and the Dma1-mediated checkpoint coordinate mitotic exit with cytokinesis to prevent premature abscission. In higher eukaryotes, integrin-linked kinase (ILK) regulates mitotic cytoskeleton dynamics and cytokinesis in retinoblastoma cells. Understanding the molecular players and regulatory circuits of mitotic cytokinesis is critical for cancer biology, developmental biology, and regenerative medicine.
regulation of mitotic cytokinesis At A Glance
| GO ID | GO:1902412 |
|---|---|
| GO term | regulation of mitotic cytokinesis |
| Ontology | biological_process |
| Synonym | regulation of cytokinesis after mitosis |
| Major function | Modulates the frequency, rate or extent of mitotic cytokinesis |
| Related processes | Mitotic exit, actomyosin ring assembly, abscission |
| Key regulators | Dma1, MEN components, ILK, myosin II |
| Disease relevance | Cancer, aneuploidy, developmental disorders |
What Is GO:1902412?
GO:1902412 regulation of mitotic cytokinesis is defined as any process that modulates the frequency, rate or extent of mitotic cytokinesis. In other words, it includes all signaling, mechanical, and temporal control mechanisms that ensure cytokinesis occurs at the right time, place, and magnitude during mitosis.
Why Is regulation of mitotic cytokinesis Important in Cell Biology?
Regulation of mitotic cytokinesis is fundamental to cell proliferation and genome stability. Defects in this process cause cytokinesis failure, resulting in tetraploidy and aneuploidy, which are hallmarks of cancer. Moreover, understanding how cytokinesis is regulated can inform strategies to manipulate cell division in regenerative contexts, such as stimulating cardiomyocyte proliferation for cardiac repair. The integration of checkpoint controls, such as the Dma1-mediated mitotic checkpoint and the MEN, ensures that cytokinesis is completed only after chromosomes are properly segregated. Thus, GO:1902412 is a nexus for cell cycle control, cytoskeletal dynamics, and disease mechanisms.
• Ensures accurate chromosome segregation and prevents aneuploidy.
• Coordinates mitotic exit with cytokinesis via checkpoint and MEN signaling.
• Involves conserved actomyosin ring mechanics from yeast to humans.
• Dysregulation leads to cancer, including retinoblastoma and other tumors.
• Modulation of cytokinesis regulators can promote cardiomyocyte proliferation.
• Provides targets for anti-cancer therapies aimed at dividing cells.
• Serves as a model for studying spatiotemporal regulation of cellular processes.
• Enables synthetic biology approaches to control cell division.
• Links to developmental disorders through cytokinesis gene mutations.
• Offers experimental tractability in yeast and mammalian cells.
What Happens During regulation of mitotic cytokinesis?
Initiation and positioning of the cleavage furrow
In simple terms: The cell decides where to pinch in two.
Regulation begins with signals from the mitotic spindle that specify the cleavage furrow position. In budding yeast, the MEN and Dma1 checkpoint coordinate the timing of furrow ingression with mitotic exit. In higher eukaryotes, RhoA and its effectors, including formins and Rho-kinase, are activated at the equatorial cortex to nucleate actin filaments and activate myosin II. Integrin-linked kinase (ILK) also contributes to mitotic cytoskeleton dynamics and furrow positioning in retinoblastoma cells.
Actomyosin ring assembly and contraction
In simple terms: A belt of actin and myosin squeezes the cell.
The actomyosin contractile ring assembles from actin filaments, myosin II, and associated proteins. Myosin II activity is regulated by phosphorylation of its regulatory light chain by Rho-kinase and other kinases. In budding yeast, the ring is composed of actin, myosin II (Myo1), and septins, and its contraction is coupled to membrane invagination. The mechanics of ring contraction are conserved and involve motor activity and filament sliding.
Membrane remodeling and abscission
In simple terms: The cell membrane is cut to separate the two cells.
After ring contraction, membrane trafficking and remodeling lead to abscission. In yeast, septum formation and membrane deposition are tightly regulated by the MEN and associated proteins. In animal cells, the ESCRT machinery mediates final abscission, and its recruitment is controlled by regulators of mitotic cytokinesis. ILK has been implicated in regulating membrane dynamics during cytokinesis in retinoblastoma cells.
Checkpoint control and temporal coordination
In simple terms: Quality control ensures division happens only when ready.
The Dma1-mediated mitotic checkpoint delays cytokinesis until chromosomes are properly segregated and mitotic exit is completed. In Saccharomyces cerevisiae, the MEN coordinates mitotic exit with cytokinesis, and its components are essential for timely abscission. This spatiotemporal regulation prevents premature cytokinesis and genomic instability.
Key Genes Involved in GO:1902412 regulation of mitotic cytokinesis
The following genes and proteins are central to the regulation of mitotic cytokinesis, as supported by the cited literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| DMA1 | Mitotic checkpoint component that coordinates mitosis with cytokinesis | Studied for checkpoint control and cytokinesis timing |
| MYO1 | Myosin II heavy chain; drives actomyosin ring contraction | Model for contractile ring mechanics |
| RHO1 | Small GTPase regulating actin organization and ring assembly | Key regulator of cytokinesis in yeast |
| CDC15 | MEN kinase; coordinates mitotic exit and cytokinesis | Central to MEN signaling |
| CDC14 | Phosphatase; regulates mitotic exit and cytokinesis | Target of MEN; controls abscission |
| ILK | Integrin-linked kinase; regulates mitotic cytoskeleton and cytokinesis | Implicated in retinoblastoma |
| RHO-kinase | Phosphorylates myosin II regulatory light chain | Regulates myosin II during cytokinesis |
| Myosin II | Motor protein; generates contractile force | Core component of actomyosin ring |
| Actin | Cytoskeletal filament; forms ring structure | Essential for ring assembly |
| Septins | Filament-forming proteins; scaffold at division site | Required for cytokinesis in yeast |
| ESCRT-III | Membrane scission machinery | Mediates abscission in animal cells |
| RhoA | GTPase; activates formins and Rho-kinase | Master regulator of furrow ingression |
| Anillin | Scaffold protein linking actin and myosin | Regulates ring stability |
| Formin | Nucleates actin filaments | Required for ring assembly |
| Cyclin B | Mitotic cyclin; regulates CDK1 activity | Controls timing of mitosis and cytokinesis |
| CDK1 | Cyclin-dependent kinase; drives mitosis | Inhibition required for mitotic exit |
| MEN components | Signaling network for mitotic exit | Essential for cytokinesis in yeast |
How Is regulation of mitotic cytokinesis Regulated?
Regulation of mitotic cytokinesis is controlled by multiple signaling pathways. In budding yeast, the mitotic exit network (MEN) and the Dma1-mediated checkpoint coordinate the timing of cytokinesis with mitotic exit. In higher eukaryotes, RhoA and its downstream effectors, including Rho-kinase and formins, regulate actomyosin ring assembly and contraction. Integrin-linked kinase (ILK) modulates mitotic cytoskeleton dynamics and cytokinesis in retinoblastoma cells. Additionally, cell cycle regulators such as CDK1 and cyclin B control the onset of mitosis and must be downregulated for cytokinesis to proceed.
regulation of mitotic cytokinesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| ILK | Retinoblastoma | ILK knockout in retinoblastoma cell lines |
| MYO1 | Cancer (cytokinesis failure) | Myo1 point mutation in yeast |
| CDC15 | Aneuploidy | CDC15 knockout in S. cerevisiae |
| DMA1 | Genomic instability | DMA1 knockout in yeast |
| Cyclin B | Cardiac regeneration | Cyclin B overexpression in cardiomyocytes |
Cancer and aneuploidy
Dysregulation of mitotic cytokinesis can lead to cytokinesis failure, resulting in tetraploidy and aneuploidy, which are common features of cancer cells. Integrin-linked kinase (ILK) has been shown to regulate mitotic cytoskeleton dynamics and cytokinesis in retinoblastoma cells, suggesting a role in tumorigenesis. Targeting cytokinesis regulators may offer therapeutic opportunities in cancers with high proliferation rates.
Cardiac regeneration
Modulation of cell cycle regulators to stimulate adult cardiomyocyte proliferation is a promising strategy for cardiac regeneration. Since cytokinesis is the final step of cell division, understanding its regulation is critical for inducing productive proliferation in cardiomyocytes.
Developmental disorders
Proper regulation of mitotic cytokinesis is essential for normal development. Mutations in cytokinesis genes can cause developmental defects due to errors in cell division and chromosome segregation. Studies in model organisms such as budding yeast have elucidated conserved mechanisms that inform human developmental biology.
From regulation of mitotic cytokinesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate cytokinesis timing? | CRISPR knockout in HeLa cells |
| How does point mutation affect actomyosin ring? | CRISPR point mutation in MYO1 in yeast |
| What is the role of ILK in retinoblastoma cytokinesis? | ILK knockout in retinoblastoma cells |
| Can overexpression of cyclin B induce cardiomyocyte proliferation? | Cyclin B overexpression in adult cardiomyocytes |
| How does Dma1 checkpoint coordinate mitosis and cytokinesis? | DMA1 knockout in S. cerevisiae |
| What is the function of MEN components in cytokinesis? | CDC15 knockout in yeast |
How to Study the regulation of mitotic cytokinesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell microscopy | Dynamics of actomyosin ring | Studying cytokinesis timing |
| CRISPR knockout | Gene function loss | Identifying essential cytokinesis genes |
| Phosphoproteomics | Phosphorylation events | Mapping signaling pathways |
| High-content screening | Phenotypic changes | Drug discovery |
| Yeast genetics | Genetic interactions | Dissecting MEN pathway |
| RNA-seq | Transcriptional changes | Identifying cytokinesis-associated genes |
| Proximity labeling | Protein-protein interactions | Mapping interactome |
| Flow cytometry | DNA content | Detecting aneuploidy |
Live-cell imaging
Live-cell microscopy allows real-time visualization of actomyosin ring assembly and contraction during mitotic cytokinesis. This method is essential for studying the spatiotemporal regulation of cytokinesis regulators such as Dma1 and MEN components.
Genetic knockout and knockdown
CRISPR knockout or RNAi knockdown of candidate genes in model organisms like S. cerevisiae or mammalian cells can reveal their roles in cytokinesis. For example, ILK knockout in retinoblastoma cells demonstrated its role in mitotic cytoskeleton regulation.
Proteomics and phosphoproteomics
Mass spectrometry-based proteomics can identify protein interactions and phosphorylation events that regulate cytokinesis. This approach has been used to study myosin II regulation by Rho-kinase and MEN signaling.
High-content screening
High-content imaging screens can identify small molecules or genes that modulate cytokinesis. Such screens are valuable for discovering new regulators and potential therapeutic targets.
How CRISPR Can Be Used to Study GO:1902412 regulation of mitotic cytokinesis
Knockout
CRISPR knockout of genes such as ILK or DMA1 can reveal their essential roles in regulation of mitotic cytokinesis. For example, ILK knockout in retinoblastoma cells impaired mitotic cytoskeleton dynamics and cytokinesis. In yeast, DMA1 knockout leads to checkpoint defects.
Point Mutation
CRISPR point mutation can mimic disease-associated or functional mutations in cytokinesis genes. For instance, point mutations in MYO1 can disrupt actomyosin ring contraction without affecting protein stability. This approach helps dissect domain-specific functions.
Knock-in
Knock-in of tagged versions of cytokinesis proteins, such as GFP-tagged Myo1 or Cdc15, allows live-cell imaging of their localization and dynamics. This is crucial for understanding spatiotemporal regulation.
Overexpression
Overexpression of regulators like cyclin B can drive cell cycle progression and cytokinesis in cells that normally do not divide, such as adult cardiomyocytes. This strategy is used to study sufficiency and to promote regeneration.
How EDITGENE Supports regulation of mitotic cytokinesis Research
Researchers studying regulation of mitotic cytokinesis-related genes often need to determine whether a candidate gene is causally involved in the process or is merely correlated. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such causal studies in relevant cell models.
Contact EDITGENE today to design your custom CRISPR model for regulation of mitotic cytokinesis research.
Frequently Asked Questions About regulation of mitotic cytokinesis
What is regulation of mitotic cytokinesis?
It is any process that modulates the frequency, rate or extent of mitotic cytokinesis, the final step of cell division.
What genes are involved in regulation of mitotic cytokinesis?
Key genes include DMA1, MYO1, CDC15, ILK, and RHO-kinase, among others.
What is the GO ID for regulation of mitotic cytokinesis?
The GO ID is GO:1902412.
How is mitotic cytokinesis regulated?
It is regulated by checkpoint controls like the Dma1-mediated checkpoint, the mitotic exit network, and RhoA signaling.
Why is regulation of mitotic cytokinesis important?
It ensures accurate chromosome segregation and prevents aneuploidy, which is linked to cancer.
What diseases are associated with defective regulation of mitotic cytokinesis?
Cancer, developmental disorders, and aneuploidy are associated with defects in cytokinesis regulation.
How can I study regulation of mitotic cytokinesis?
Using live-cell imaging, CRISPR knockout, proteomics, and high-content screening.
What model organisms are used to study regulation of mitotic cytokinesis?
Saccharomyces cerevisiae and mammalian cell lines are commonly used.
What is the role of ILK in cytokinesis?
ILK regulates mitotic cytoskeleton dynamics and cytokinesis in retinoblastoma cells.
Can CRISPR be used to study regulation of mitotic cytokinesis?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression are powerful approaches.
Conclusion
Regulation of mitotic cytokinesis (GO:1902412) is a critical biological process that ensures proper cell division and genomic stability. Its dysregulation is implicated in cancer and developmental disorders, making it a key area of research. Advances in CRISPR-based models and imaging techniques continue to unravel the complex regulatory networks, offering potential for therapeutic interventions.
References
- 1. Cullati SN et al.. 2019. Spatiotemporal regulation of the Dma1-mediated mitotic checkpoint coordinates mitosis with cytokinesis.. Curr Genet 65(3):663-668 PMID: 30600396
- 2. Mohamed TMA et al.. 2018. Regulation of Cell Cycle to Stimulate Adult Cardiomyocyte Proliferation and Cardiac Regeneration.. Cell 173(1):104-116.e12 PMID: 29502971
- 3. Robinson DN et al.. 2004. Mechanics and regulation of cytokinesis.. Curr Opin Cell Biol 16(2):182-8 PMID: 15196562
- 4. Baro B et al.. 2017. Regulation of Mitotic Exit in Saccharomyces cerevisiae.. Methods Mol Biol 1505:3-17 PMID: 27826852
- 5. Bhavsar-Jog YP et al.. 2017. Mechanics and regulation of cytokinesis in budding yeast.. Semin Cell Dev Biol 66:107-118 PMID: 28034796
- 6. Matsumura F. 2005. Regulation of myosin II during cytokinesis in higher eukaryotes.. Trends Cell Biol 15(7):371-7 PMID: 15935670
- 7. Foltman M et al.. 2017. Studying the Role of the Mitotic Exit Network in Cytokinesis.. Methods Mol Biol 1505:245-262 PMID: 27826869
- 8. Sikkema WK et al.. 2014. Regulation of mitotic cytoskeleton dynamics and cytokinesis by integrin-linked kinase in retinoblastoma cells.. PLoS One 9(6):e98838 PMID: 24911651
