GO:1902410 mitotic cytokinetic process: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1902410 (mitotic cytokinetic process) describes the final step of mitosis in which the cytoplasm is physically divided between two daughter cells.
• The process is driven by an actomyosin contractile ring, membrane remodeling, and the ESCRT-III machinery that executes abscission.
• Key regulators include PLK1, the ESCRT-III subunit CHMP4C, Rab14/MACF2, and integrin adhesion complexes.
• Failure of abscission can cause genome instability, a hallmark of cancer and a target for therapeutic intervention.
• CRISPR knockout, point mutation, knock-in, and overexpression models are essential to dissect gene function in mitotic cytokinesis.
• EDITGENE provides end-to-end CRISPR services, including library screening and bioinformatics, to accelerate cytokinetic research.
Description
Mitotic cytokinetic process (GO:1902410) is the biological process that physically separates the cytoplasm of a dividing cell into two daughter cells after chromosome segregation. It is a highly coordinated event that ensures genomic integrity and is essential for development, tissue homeostasis, and tumor suppression. Defects in this process lead to binucleation, aneuploidy, and cancer, making it a critical area of cell biology research. The process involves the assembly and constriction of an actomyosin ring, membrane trafficking, and the final scission step known as abscission, which is executed by the ESCRT machinery. Recent studies have revealed that proteins such as AGO2 and Rab14 are compartmentalized to the cytokinetic bridge and midbody, highlighting the complexity of this process. Understanding the molecular players and their regulation is vital for developing targeted therapies against diseases linked to cytokinesis failure. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a comprehensive overview of GO:1902410, its genes, functions, and research methodologies.
mitotic cytokinetic process At A Glance
| GO ID | GO:1902410 |
|---|---|
| GO term | mitotic cytokinetic process |
| Ontology | biological_process |
| Synonym | None |
| Major function | Physical separation of daughter cells during mitosis |
| Key structures | Actomyosin contractile ring, midbody, cytokinetic bridge, abscission site |
| Key regulators | PLK1, ESCRT-III (CHMP4C), Rab14/MACF2, integrins |
| Related diseases | Cancer, genome instability, developmental disorders |
What Is GO:1902410?
According to the Gene Ontology, GO:1902410 (mitotic cytokinetic process) is defined as any cytokinetic process that is involved in the mitotic cell cycle. In simpler terms, it encompasses all the cellular events that lead to the physical division of a mitotic cell into two daughter cells, including contractile ring formation, ingression, midbody formation, and abscission.
Why Is mitotic cytokinetic process Important in Cell Biology?
Mitotic cytokinetic process is fundamental to life because it ensures that each daughter cell receives a complete copy of the genome and appropriate cytoplasmic contents. Errors in this process result in tetraploidy or aneuploidy, which are hallmarks of cancer and are associated with tumor progression and chemoresistance. Moreover, cytokinesis is a potential therapeutic target, as rapidly dividing cancer cells are particularly sensitive to perturbations in cell division. Understanding the molecular mechanisms of cytokinesis also sheds light on developmental processes, stem cell renewal, and tissue regeneration.
• Ensures genomic stability by preventing binucleation and aneuploidy.
• Essential for normal development and tissue homeostasis.
• Dysregulation is linked to cancer, including breast, liver, and colorectal cancers.
• Provides targets for anti-cancer drugs that inhibit cytokinesis.
• Involves ESCRT-III machinery, which is implicated in neurodegeneration and viral budding.
• Requires precise spatiotemporal regulation by kinases such as PLK1.
• Crosstalk with membrane trafficking pathways (Rab14/MACF2) influences abscission timing.
• Integrin-mediated adhesion to the extracellular matrix modulates abscission and genome integrity.
• Tension forces from the environment can trigger abscission in fibroblasts.
• Non-canonical roles of RNAi components (AGO2) in cytokinesis have been discovered.
What Happens During mitotic cytokinetic process?
Contractile Ring Assembly and Ingression
In simple terms: The cell builds a belt of actin and myosin that tightens to pinch the cell in two.
During anaphase, the mitotic spindle signals the assembly of an actomyosin contractile ring at the equatorial cortex. This ring is composed of actin filaments, myosin II, and associated proteins such as anillin and septins. The small GTPase RhoA activates formin and ROCK to promote actin polymerization and myosin activation, leading to ring constriction and cleavage furrow ingression. PLK1 regulates multiple steps of cytokinesis, including contractile ring formation and abscission.
Midbody Formation and Membrane Remodeling
In simple terms: The narrow bridge between daughter cells becomes a signaling hub called the midbody.
As the cleavage furrow ingresses, the central spindle microtubules bundle to form the midbody, a dense structure that serves as a platform for abscission regulators. Membrane trafficking pathways, including Rab14/MACF2-mediated endosomal targeting, deliver lipids and proteins to the intercellular bridge to facilitate abscission. The midbody also recruits ESCRT components, such as CHMP4C, which are essential for the final scission step.
Abscission and ESCRT-III Function
In simple terms: The ESCRT machinery cuts the final thread connecting the two cells.
Abscission is the final step of cytokinesis, where the thin intercellular bridge is severed. The ESCRT-III complex, including CHMP4C, polymerizes into filaments that constrict and scission the membrane. A cancer-associated polymorphism in CHMP4C disrupts the abscission checkpoint, leading to genome instability. PLK1 phosphorylates ESCRT-III components to regulate abscission timing.
Regulation by Tension and Adhesion
In simple terms: Physical forces and cell adhesion can influence when and how abscission occurs.
Integrin-mediated adhesion to the extracellular matrix contributes to cytokinetic abscission and genomic integrity. Tension-induced abscission has been observed in human fibroblasts, where mechanical forces trigger the final scission step. These findings highlight the interplay between mechanical cues and biochemical pathways in cytokinesis.
Non-canonical Roles of RNAi Components
In simple terms: Proteins usually involved in RNA interference also help control cytokinesis.
AGO2, a core component of the RNA-induced silencing complex, is compartmentalized to the centrosome, mitotic spindle, and cytokinetic bridge in human liver cells, suggesting a non-canonical, RNAi-dependent control of local homeostasis during mitosis. This expands the known functions of RNAi machinery beyond gene silencing.
Key Genes Involved in GO:1902410 mitotic cytokinetic process
The following genes and proteins are key players in the mitotic cytokinetic process, as supported by verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PLK1 | Kinase regulating contractile ring formation and abscission | Target for anti-mitotic drugs; regulates ESCRT-III |
| CHMP4C | ESCRT-III subunit; abscission checkpoint | Polymorphism linked to cancer and genome instability |
| Rab14 | Endosomal targeting during cytokinesis | Regulates membrane trafficking for abscission |
| MACF2 | Partner of Rab14 in endosomal targeting | Complex with Rab14 controls abscission |
| AGO2 | RNAi component; localizes to cytokinetic bridge | Non-canonical role in mitosis |
| Integrins | Cell adhesion receptors | Modulate abscission and genomic integrity |
| ESCRT-III | Membrane scission machinery | Central to abscission; linked to cancer |
| RhoA | GTPase activating contractile ring | Master regulator of cytokinesis |
| Anillin | Actin-binding protein in contractile ring | Scaffold for ring assembly |
| Myosin II | Motor protein for ring contraction | Force generation for ingression |
| Actin | Cytoskeletal filament | Contractile ring component |
| Septins | Filament-forming proteins | Stabilize the cleavage furrow |
| Cep55 | Midbody protein | Recruits ESCRT machinery |
| ALIX | ESCRT-associated protein | Facilitates abscission |
| TSG101 | ESCRT-I component | Required for abscission |
| VPS4 | AAA-ATPase | Recycles ESCRT-III |
| Spastin | Microtubule-severing enzyme | Required for midbody microtubule disassembly |
How Is mitotic cytokinetic process Regulated?
The mitotic cytokinetic process is tightly regulated by phosphorylation, ubiquitination, and mechanical forces. PLK1 is a key kinase that controls multiple steps, including contractile ring assembly and abscission, through phosphorylation of substrates such as ESCRT-III components. The ESCRT-III abscission checkpoint delays scission in response to chromatin bridges or nuclear defects, preventing genome instability. Rab14/MACF2-mediated endosomal trafficking regulates membrane delivery to the intercellular bridge. Integrin-mediated adhesion and tension also modulate abscission timing and fidelity. Additionally, non-canonical RNAi components like AGO2 may contribute to local homeostasis at the cytokinetic bridge.
mitotic cytokinetic process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CHMP4C | Cancer, genome instability | Knock-in of cancer-associated polymorphism in cell lines |
| PLK1 | Cancer, mitotic defects | Knockout or overexpression in cancer cell lines |
| Rab14 | Cancer, membrane trafficking defects | Knockout in HeLa cells |
| Integrins | Cancer, developmental disorders | Knockout in fibroblasts |
| AGO2 | Cancer, RNAi dysfunction | Knockout in liver cancer cells |
Cancer and Genome Instability
Defects in mitotic cytokinetic process lead to binucleation, aneuploidy, and chromosomal instability, which are hallmarks of cancer. A cancer-associated polymorphism in CHMP4C disrupts the abscission checkpoint, promoting genome instability. Overexpression of PLK1 is observed in many cancers and is associated with poor prognosis. Targeting cytokinesis regulators is a promising anti-cancer strategy.
Developmental Disorders
Proper cytokinesis is essential for embryonic development and tissue morphogenesis. Mutations in cytokinesis genes can cause developmental disorders, although specific diseases are still being defined. Integrin-mediated adhesion defects during cytokinesis may contribute to developmental abnormalities.
Neurodegeneration
The ESCRT machinery, which is central to abscission, is also involved in neuronal maintenance and its dysfunction is linked to neurodegenerative diseases such as amyotrophic lateral sclerosis and frontotemporal dementia. However, direct links between cytokinetic ESCRT function and neurodegeneration require further investigation.
From mitotic cytokinetic process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate abscission? | CRISPR knockout in HeLa or U2OS cells followed by live-cell imaging |
| Does a point mutation in CHMP4C affect abscission checkpoint? | Knock-in of mutant CHMP4C in diploid cells |
| How does PLK1 phosphorylation control cytokinesis? | Point mutation of PLK1 phosphorylation sites |
| What is the role of Rab14 in membrane trafficking during cytokinesis? | Knockout and rescue with tagged Rab14 |
| Does AGO2 localize to the cytokinetic bridge? | Tagged knock-in of AGO2 with fluorescent protein |
| How does tension affect abscission? | Overexpression of mechanosensitive proteins in fibroblasts |
How to Study the mitotic cytokinetic process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Dynamics of contractile ring and abscission | Visualize cytokinesis in real time |
| CRISPR knockout | Gene function in cytokinesis | Identify essential genes |
| Proximity labeling (BioID) | Protein interactions at midbody | Map local interactome |
| Immunofluorescence | Localization of proteins to midbody | Validate candidate genes |
| RNA-seq | Transcriptional changes upon cytokinesis failure | Identify pathways affected |
| Phosphoproteomics | Kinase substrates during mitosis | Map PLK1 targets |
| Tension sensors (FRET) | Mechanical forces at cleavage furrow | Study tension-induced abscission |
Live-Cell Imaging
Live-cell imaging with fluorescently tagged proteins (e.g., GFP-actin, mCherry-ESCRT-III) allows real-time visualization of contractile ring dynamics, midbody formation, and abscission. This method is essential for assessing the timing and fidelity of cytokinesis in response to genetic perturbations.
CRISPR-Based Genetic Screens
Genome-wide CRISPR knockout screens can identify novel regulators of cytokinesis by selecting for cells that survive or exhibit specific phenotypes, such as binucleation. These screens are powerful for discovering new genes involved in abscission and genome stability.
Proteomics and Interactomics
Affinity purification coupled with mass spectrometry (AP-MS) can identify protein-protein interactions at the midbody and cytokinetic bridge. Proximity labeling (BioID) can map the local proteome of the intercellular bridge, revealing new components.
RNA Interference and CRISPR Interference
RNAi and CRISPRi knockdown of candidate genes followed by immunofluorescence for midbody markers (e.g., Cep55, CHMP4C) can rapidly assess their role in cytokinesis. These methods are complementary to knockout approaches.
How CRISPR Can Be Used to Study GO:1902410 mitotic cytokinetic process
Knockout
CRISPR knockout of genes such as PLK1, CHMP4C, or Rab14 in cell lines (e.g., HeLa, U2OS) can reveal their essential roles in cytokinesis. For example, CHMP4C knockout leads to abscission checkpoint defects and genome instability. Knockout of Rab14 impairs endosomal targeting and abscission.
Point Mutation
Introducing point mutations via CRISPR base editing or HDR can model cancer-associated polymorphisms, such as the CHMP4C variant that disrupts the abscission checkpoint. Point mutations in PLK1 phosphorylation sites can dissect its specific roles in cytokinesis.
Knock-in
Knock-in of fluorescent tags (e.g., GFP, mCherry) into endogenous loci allows real-time tracking of proteins like AGO2 at the cytokinetic bridge. Knock-in of mutant alleles can also model disease-associated variants.
Overexpression
Overexpression of cytokinesis regulators, such as PLK1 or ESCRT-III components, can induce aberrant cytokinesis and is useful for studying gain-of-function effects. Overexpression of mechanosensitive proteins can mimic tension-induced abscission.
How EDITGENE Supports mitotic cytokinetic process Research
Researchers studying mitotic cytokinetic process-related genes often need to determine whether a candidate gene is causally involved in abscission, contractile ring dynamics, or genome stability. EDITGENE provides a comprehensive suite of CRISPR services to accelerate this research, from knockout to knock-in and library screening.
Contact EDITGENE today to design your custom CRISPR model for mitotic cytokinetic process research.
Frequently Asked Questions About mitotic cytokinetic process
What is GO:1902410 mitotic cytokinetic process?
GO:1902410 is a Gene Ontology term for any cytokinetic process involved in the mitotic cell cycle, including contractile ring formation, ingression, and abscission.
What genes are involved in mitotic cytokinetic process?
Key genes include PLK1, CHMP4C, Rab14, MACF2, AGO2, and integrins, among others.
What is the role of ESCRT-III in cytokinesis?
ESCRT-III mediates the final membrane scission step called abscission, and its dysfunction leads to genome instability.
How is abscission regulated?
Abscission is regulated by PLK1 phosphorylation, the ESCRT-III checkpoint, Rab14/MACF2 trafficking, and mechanical tension.
What diseases are linked to cytokinesis defects?
Cytokinesis defects are linked to cancer, genome instability, and potentially developmental disorders.
What methods are used to study mitotic cytokinetic process?
Live-cell imaging, CRISPR screens, proteomics, and immunofluorescence are commonly used.
Can CRISPR knockout be used to study cytokinesis genes?
Yes, CRISPR knockout of genes like PLK1 and CHMP4C has revealed essential roles in cytokinesis.
What is the abscission checkpoint?
The abscission checkpoint delays abscission in response to chromatin bridges or nuclear defects to prevent genome instability.
How does PLK1 regulate cytokinesis?
PLK1 phosphorylates multiple substrates, including ESCRT-III components, to control contractile ring assembly and abscission.
What is the role of AGO2 in cytokinesis?
AGO2 localizes to the cytokinetic bridge and may have a non-canonical, RNAi-dependent role in local homeostasis during mitosis.
Conclusion
The mitotic cytokinetic process (GO:1902410) is a fundamental biological process that ensures faithful cell division and genomic stability. Its dysregulation is implicated in cancer and other diseases, making it a critical area of research. Advances in CRISPR technology and imaging have illuminated the molecular players, including PLK1, ESCRT-III, and Rab14. EDITGENE's comprehensive CRISPR services empower researchers to dissect these mechanisms and develop novel therapeutic strategies.
References
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- 2. Sadler JBA et al.. 2018. A cancer-associated polymorphism in ESCRT-III disrupts the abscission checkpoint and promotes genome instability.. Proc Natl Acad Sci U S A 115(38):E8900-E8908 PMID: 30181294
- 3. Gatta AT et al.. 2019. The ESCRT-machinery: closing holes and expanding roles.. Curr Opin Cell Biol 59:121-132 PMID: 31132588
- 4. Fededa JP et al.. 2012. Molecular control of animal cell cytokinesis.. Nat Cell Biol 14(5):440-7 PMID: 22552143
- 5. Colicino EG et al.. 2018. Regulating a key mitotic regulator, polo-like kinase 1 (PLK1).. Cytoskeleton (Hoboken) 75(11):481-494 PMID: 30414309
- 6. Gibieža P et al.. 2021. Rab14/MACF2 complex regulates endosomal targeting during cytokinesis.. Mol Biol Cell 32(7):554-566 PMID: 33566684
- 7. Rani B et al.. 2022. Contribution of integrin adhesion to cytokinetic abscission and genomic integrity.. Front Cell Dev Biol 10:1048717 PMID: 36578785
- 8. Gupta DK et al.. 2018. Tension-induced cytokinetic abscission in human fibroblasts.. Oncotarget 9(10):8999-9009 PMID: 29507669
