GO:0032465 regulation of cytokinesis: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0032465 regulation of cytokinesis describes any process that modulates the frequency, rate or extent of the division of the cytoplasm and separation into two daughter cells.
• Cytokinesis is driven by an actomyosin contractile ring in animal and fungal cells, whose assembly and constriction are tightly regulated in space and time.
• RhoA is a master regulator of contractile ring formation and constriction in animal cells, cycling between active GTP-bound and inactive GDP-bound states.
• In bacteria, FtsZ and its accessory proteins form the division ring and are key targets for understanding regulation of cytokinesis.
• In plants, the mitogen-activated protein kinase cascade regulates microtubule organization and function during cytokinesis.
• Dysregulation of cytokinesis is linked to cancer, developmental defects, and other diseases, making it a target for CRISPR-based functional studies.
Description
Cytokinesis is the final step of cell division, physically separating the cytoplasm of a dividing cell into two daughter cells. The regulation of cytokinesis (GO:0032465) encompasses all processes that modulate the frequency, rate, or extent of this division and separation. This regulation is essential for maintaining genome stability, cell proliferation, and tissue homeostasis. Research into cytokinesis regulation spans bacteria, fungi, plants, and animals, revealing both conserved and organism-specific mechanisms. Understanding how cytokinesis is controlled is critical for uncovering the molecular basis of diseases such as cancer, where cytokinesis failure can lead to aneuploidy and tumorigenesis. Moreover, cytokinesis regulators are potential targets for therapeutic intervention and for biotechnological applications. This article provides a comprehensive overview of the regulation of cytokinesis, integrating authoritative GO annotations with published literature to support researchers in designing experiments and interpreting data.
regulation of cytokinesis At A Glance
| GO ID | GO:0032465 |
|---|---|
| GO term | regulation of cytokinesis |
| Ontology | biological_process |
| Synonym | regulation of cell cycle cytokinesis |
| Major function | Modulates the frequency, rate, or extent of cytoplasmic division and daughter cell separation |
| Organisms | Bacteria, fungi, plants, animals |
| Key regulators | RhoA, FtsZ, anillin, myosin II, MAPK cascade |
| Disease relevance | Cancer, developmental disorders, aneuploidy |
What Is GO:0032465?
According to the Gene Ontology, GO:0032465 regulation of cytokinesis is defined as any process that modulates the frequency, rate or extent of the division of the cytoplasm of a cell and its separation into two daughter cells. In other words, it includes all molecular events that control when, where, and how efficiently cytokinesis occurs, ensuring proper cell division.
Why Is regulation of cytokinesis Important in Cell Biology?
Regulation of cytokinesis is fundamental to all life, as it ensures the faithful segregation of genetic material and cytoplasmic contents during cell division. Defects in cytokinesis regulation can lead to binucleation, aneuploidy, and cell death, contributing to diseases such as cancer and developmental abnormalities. Moreover, cytokinesis is a target for antibiotics and anticancer drugs, and understanding its regulation can inform the development of new therapeutics.
• Ensures proper cell division and genome stability.
• Prevents aneuploidy and tumorigenesis.
• Essential for development and tissue homeostasis.
• Target for antibacterial and anticancer therapies.
• Involved in cell repair and wound healing.
• Regulated by RhoA signaling in animal cells.
• Requires precise spatial and temporal control.
• In plants, linked to MAPK signaling and microtubule organization.
• Dysregulation associated with apoptosis and ubiquitin-ligase pathways.
• Provides insights into evolution of cell division mechanisms.
What Happens During regulation of cytokinesis?
Initiation and positioning of the division site
In simple terms: The cell decides where to split.
In many organisms, the position of the division site is determined by the assembly of a contractile ring or a division septum. In fission yeast, Mid1/anillin is a key factor that marks the medial region and recruits other components for ring assembly. In animal cells, RhoA activation at the equatorial cortex specifies the cleavage furrow. In bacteria, FtsZ polymerizes into a ring at midcell, guided by accessory proteins.
Assembly of the actomyosin contractile ring
In simple terms: A ring of actin and myosin forms to pinch the cell.
The contractile ring is composed of actin filaments, myosin II, and many associated proteins. Its assembly is regulated by RhoA and its effectors, which promote actin polymerization and myosin activation. In higher eukaryotes, myosin II regulatory light chain phosphorylation is crucial for ring contraction. The ring is dynamic and undergoes constant remodeling.
Constriction and disassembly of the ring
In simple terms: The ring tightens and then breaks down.
Once assembled, the contractile ring constricts, driven by myosin motor activity and actin depolymerization. This process is tightly regulated to ensure complete separation. In animal cells, RhoA activity must be downregulated for ring disassembly and abscission. In bacteria, FtsZ ring constriction is coupled to peptidoglycan synthesis.
Membrane remodeling and abscission
In simple terms: The cell membrane pinches off to separate the two cells.
After ring constriction, the plasma membrane must be remodeled to complete separation. In animal cells, this involves the ESCRT machinery and other factors. The anti-apoptotic E2/E3 ubiquitin-ligase BRUCE has been implicated in regulating both apoptosis and cytokinesis, linking these processes. In plants, the cell plate is formed instead of a contractile ring, guided by microtubules and MAPK signaling.
Spatial and temporal regulation
In simple terms: The cell controls when and where division happens.
Regulation of cytokinesis requires precise spatial and temporal coordination. In fission yeast, Mid1/anillin ensures the ring forms only at the correct location. In animal cells, RhoA activity is restricted to the equatorial zone by centralspindlin and other factors. In plants, the MAPK cascade regulates microtubule organization during cell plate formation.
Key Genes Involved in GO:0032465 regulation of cytokinesis
The following genes and proteins are key players in the regulation of cytokinesis across model organisms.
| Gene | Major Role | Research Relevance |
|---|---|---|
| RhoA | Master regulator of contractile ring assembly and constriction | Target for studying cytokinesis in animal cells |
| FtsZ | Bacterial cell division ring protein | Antibacterial drug target |
| Myosin II | Motor protein driving ring contraction | Regulation by phosphorylation |
| Anillin | Scaffold protein linking RhoA to the ring | Spatial regulation in fission yeast |
| Mid1 | Anillin homolog in fission yeast | Division site positioning |
| BRUCE | E2/E3 ubiquitin-ligase | Links apoptosis and cytokinesis |
| MAPK cascade components | Regulate microtubules in plant cytokinesis | Plant cell division |
| Actin | Structural component of the ring | Ring assembly and mechanics |
| Formin | Nucleates actin filaments | Ring assembly |
| Profilin | Regulates actin polymerization | Ring dynamics |
| Cofilin | Actin depolymerization | Ring disassembly |
| Anillin | Links actin and myosin | Ring stability |
| RhoGEF | Activates RhoA | Spatial regulation |
| RhoGAP | Inactivates RhoA | Temporal regulation |
| Citron kinase | RhoA effector | Ring constriction |
| mDia | Formin, RhoA effector | Actin nucleation |
| ROCK | RhoA effector, activates myosin | Ring contraction |
How Is regulation of cytokinesis Regulated?
Regulation of cytokinesis is itself regulated by upstream signaling pathways. In animal cells, the small GTPase RhoA is controlled by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), which are spatially and temporally regulated. In plants, the mitogen-activated protein kinase (MAPK) cascade regulates microtubule organization and function during cytokinesis. In bacteria, FtsZ assembly is regulated by accessory proteins such as FtsA and ZipA. Additionally, ubiquitin-ligase BRUCE has been shown to regulate cytokinesis, linking it to apoptotic pathways.
regulation of cytokinesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| RhoA | Cancer, cell proliferation | Knockout in cancer cell lines |
| BRUCE | Cancer, apoptosis | Overexpression in HeLa cells |
| FtsZ | Bacterial infections | Knockout in E. coli |
| MAPK cascade | Plant growth defects | Knockout in Arabidopsis |
| Anillin | Developmental disorders | Knockdown in zebrafish |
Cytokinesis failure and cancer
Defects in the regulation of cytokinesis can lead to tetraploidy and aneuploidy, which are hallmarks of cancer. For example, dysregulation of RhoA signaling or contractile ring components can cause cytokinesis failure and genomic instability. The anti-apoptotic protein BRUCE, which regulates cytokinesis, is often overexpressed in tumors, suggesting a link between cytokinesis regulation and cancer.
Developmental disorders
Proper regulation of cytokinesis is essential for embryonic development. Mutations in genes involved in cytokinesis, such as those encoding contractile ring components, can cause developmental defects. In plants, disruption of MAPK signaling during cytokinesis leads to abnormal cell plate formation and growth defects.
Infectious diseases
Bacterial cytokinesis is a target for antibiotics. FtsZ and its accessory proteins are essential for bacterial division, and inhibitors of FtsZ assembly are being explored as antibacterial agents.
From regulation of cytokinesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate cytokinesis? | Knockout cell line |
| Does mutation Y affect cytokinesis? | Point mutation knock-in |
| Where does protein X localize during cytokinesis? | Tagged knock-in (e.g., GFP) |
| Does overexpression of gene X cause cytokinesis defects? | Overexpression cell line |
| What is the role of gene X in cytokinesis? | CRISPR library screening |
| How does gene X affect cytokinesis transcriptome? | RNA-seq after knockout |
How to Study the regulation of cytokinesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Dynamics of ring assembly and constriction | Studying cytokinesis in real time |
| CRISPR knockout | Loss-of-function effects | Identifying essential regulators |
| RNA-seq | Transcriptional changes | Pathway analysis after gene perturbation |
| Proteomics | Protein interactions and composition | Identifying ring components |
| FRET biosensors | RhoA activity | Spatiotemporal regulation |
| Electron microscopy | Ultrastructure of division site | Bacterial cytokinesis |
| Flow cytometry | Cell cycle and ploidy | Detecting cytokinesis failure |
Live-cell imaging
Live-cell imaging using fluorescently tagged proteins (e.g., GFP-actin, GFP-myosin) allows real-time visualization of contractile ring assembly and constriction. This method is essential for studying the dynamics of cytokinesis regulation.
RNA interference and CRISPR screens
High-throughput RNAi or CRISPR screens can identify genes that regulate cytokinesis. For example, genome-wide screens have uncovered novel regulators of cytokinesis in human cells.
Proteomics
Mass spectrometry-based proteomics can identify proteins that associate with the contractile ring or the midbody, providing insights into the molecular composition and regulation of cytokinesis.
Biochemical assays
In vitro assays using purified proteins can reconstitute aspects of cytokinesis, such as actin polymerization or myosin motor activity, to study regulation at the molecular level.
How CRISPR Can Be Used to Study GO:0032465 regulation of cytokinesis
Knockout
CRISPR knockout of genes such as RhoA or FtsZ can reveal their essential roles in cytokinesis. For example, RhoA knockout in human cells leads to cytokinesis failure and binucleation. In bacteria, FtsZ knockout is lethal, confirming its essential function.
Point Mutation
Point mutations can be introduced to study specific residues required for cytokinesis regulation. For instance, mutating the phosphorylation sites of myosin II regulatory light chain can affect ring contraction.
Knock-in
Knock-in of tagged proteins (e.g., GFP-RhoA) allows visualization of protein localization and dynamics during cytokinesis. This approach has been used to study anillin localization in fission yeast.
Overexpression
Overexpression of cytokinesis regulators can cause defects. For example, overexpression of BRUCE affects both apoptosis and cytokinesis. Overexpression of constitutively active RhoA leads to ectopic furrow formation.
How EDITGENE Supports regulation of cytokinesis Research
Researchers studying regulation of cytokinesis-related genes often need to determine whether a candidate gene is causally involved in the process, and what its precise function is. This requires robust genetic models, such as knockout, point mutation, knock-in, and overexpression cell lines, as well as high-throughput screening and bioinformatics analysis. EDITGENE provides a comprehensive suite of services to accelerate such research.
Contact EDITGENE today to design your custom CRISPR model for regulation of cytokinesis research.
Frequently Asked Questions About regulation of cytokinesis
What is regulation of cytokinesis?
Regulation of cytokinesis (GO:0032465) refers to any process that modulates the frequency, rate or extent of the division of the cytoplasm and separation into two daughter cells.
What genes are involved in regulation of cytokinesis?
Key genes include RhoA, FtsZ, myosin II, anillin, and components of the MAPK cascade, among others.
How is cytokinesis regulated in animal cells?
In animal cells, cytokinesis is regulated by RhoA signaling, which controls actomyosin contractile ring assembly and constriction.
What is the role of RhoA in cytokinesis?
RhoA is a master regulator that promotes actin polymerization and myosin activation at the cleavage furrow.
How do bacteria regulate cytokinesis?
Bacteria regulate cytokinesis through FtsZ and its accessory proteins, which form the division ring.
What happens when cytokinesis is dysregulated?
Dysregulation can lead to aneuploidy, cancer, and developmental defects.
What methods are used to study regulation of cytokinesis?
Methods include live-cell imaging, CRISPR screens, proteomics, and biochemical assays.
Can CRISPR be used to study cytokinesis?
Yes, CRISPR knockout, knock-in, and point mutation models are powerful tools for studying cytokinesis regulation.
What is the contractile ring?
The contractile ring is a dynamic structure of actin and myosin that constricts to divide the cell.
How does plant cytokinesis differ from animal cytokinesis?
Plant cells form a cell plate instead of a contractile ring, regulated by MAPK signaling and microtubules.
Conclusion
Regulation of cytokinesis (GO:0032465) is a fundamental biological process that ensures proper cell division across all domains of life. Its dysregulation is linked to cancer, developmental disorders, and other diseases. Advances in CRISPR-based models and screening technologies are accelerating our understanding of the molecular mechanisms controlling cytokinesis. EDITGENE provides essential tools and services to support this research, from knockout and knock-in cell lines to library screening and bioinformatics.
References
- 1. Wang M et al.. 2020. Regulation of cytokinesis: FtsZ and its accessory proteins.. Curr Genet 66(1):43-49 PMID: 31209564
- 2. Basant A et al.. 2018. Spatiotemporal Regulation of RhoA during Cytokinesis.. Curr Biol 28(9):R570-R580 PMID: 29738735
- 4. Matsumura F. 2005. Regulation of myosin II during cytokinesis in higher eukaryotes.. Trends Cell Biol 15(7):371-7 PMID: 15935670
- 5. Dekraker C et al.. 2018. Regulation and Assembly of Actomyosin Contractile Rings in Cytokinesis and Cell Repair.. Anat Rec (Hoboken) 301(12):2051-2066 PMID: 30312008
- 6. Rincon SA et al.. 2012. Mid1/anillin and the spatial regulation of cytokinesis in fission yeast.. Cytoskeleton (Hoboken) 69(10):764-77 PMID: 22888038
- 7. Sasabe M et al.. 2012. Regulation of organization and function of microtubules by the mitogen-activated protein kinase cascade during plant cytokinesis.. Cytoskeleton (Hoboken) 69(11):913-8 PMID: 23027702
- 8. Pohl C et al.. 2008. Regulation of apoptosis and cytokinesis by the anti-apoptotic E2/E3 ubiquitin-ligase BRUCE.. Ernst Schering Found Symp Proc PMID: 19198067
