GO:1902850 microtubule cytoskeleton organization involved in mitosis: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1902850 describes any microtubule cytoskeleton organization that is involved in mitosis, encompassing spindle assembly, kinetochore-microtubule attachment, and mitotic microtubule dynamics [1,6].
• The process is driven by microtubule-associated proteins (MAPs), motor proteins, and kinases that regulate microtubule nucleation, stability, and sliding [1,7].
• Phase separation of centrosomal and spindle proteins contributes to mitotic microtubule organization and spindle assembly.
• Dysregulation of mitotic microtubule organization is linked to cancer, neurodevelopmental disorders, and chemotherapy resistance [2,8].
• Key genes include PLK4, TRIM37, and components of the kinetochore-microtubule interface such as NDC80 and SKA complexes [2,6].
• CRISPR knockout, point mutation, knock-in, and overexpression models enable functional dissection of mitotic microtubule organization genes [2,7].
Description
Microtubule cytoskeleton organization involved in mitosis (GO:1902850) is a biological process that encompasses all microtubule cytoskeleton organization events specifically required for mitosis. This includes the assembly and disassembly of the mitotic spindle, the attachment of kinetochores to microtubules, and the dynamic reorganization of microtubule arrays that ensures accurate chromosome segregation. The process is fundamental to cell division and is tightly regulated by a network of microtubule-associated proteins (MAPs), motor proteins, and mitotic kinases [1,7]. Researchers study GO:1902850 to understand the molecular mechanisms of mitosis, to identify targets for cancer therapy, and to model diseases caused by mitotic defects [2,8]. The term is distinct from general microtubule cytoskeleton organization because it is spatially and temporally restricted to mitosis, involving specialized structures such as the spindle apparatus and the kinetochore-microtubule interface. Defects in this process lead to aneuploidy, genomic instability, and cell death, making it a critical area of investigation in cell biology and oncology [2,8].
microtubule cytoskeleton organization involved in mitosis At A Glance
| GO ID | GO:1902850 |
|---|---|
| GO term | microtubule cytoskeleton organization involved in mitosis |
| Ontology | biological_process |
| Synonym | microtubule cytoskeleton organisation involved in mitosis; microtubule cytoskeleton organization and biogenesis involved in mitosis; microtubule dynamics involved in mitosis |
| Major function | Assembly, remodeling, and disassembly of microtubule-based structures during mitosis, including the mitotic spindle and kinetochore-microtubule attachments [1,6] |
| Key cellular structures | Mitotic spindle, centrosomes, kinetochores, and microtubule arrays [1,6,8] |
| Key regulators | Microtubule-associated proteins (MAPs), motor proteins (kinesins, dyneins), and mitotic kinases (e.g., PLK4, Aurora kinases) [1,2,7] |
| Disease relevance | Cancer, neurodevelopmental disorders, and chemoresistance [2,8] |
What Is GO:1902850?
GO:1902850 is defined as any microtubule cytoskeleton organization that is involved in mitosis. In other words, it covers the full set of cellular events that build, maintain, and remodel microtubule-based structures during cell division, including spindle formation, kinetochore-microtubule attachment, and the dynamic instability of mitotic microtubules [1,6].
Why Is microtubule cytoskeleton organization involved in mitosis Important in Cell Biology?
GO:1902850 is essential for accurate chromosome segregation and genomic stability. Disruption of mitotic microtubule organization leads to aneuploidy, which is a hallmark of cancer and a driver of tumor evolution [2,8]. Moreover, proteins involved in this process are targets of chemotherapeutic agents such as taxanes and vinca alkaloids, and understanding their regulation can inform the development of new anticancer strategies. The process also plays a role in neurodevelopment, as mutations in mitotic microtubule regulators cause microcephaly and other brain disorders.
• Ensures faithful chromosome segregation and prevents aneuploidy [2,6].
• Provides targets for anticancer drugs that interfere with microtubule dynamics.
• Involved in the pathogenesis of microcephaly and neurodevelopmental disorders.
• Regulates cell cycle progression and checkpoint control.
• Contributes to tissue homeostasis and development.
• Dysregulation leads to chemoresistance in breast and other cancers.
• Studied using model organisms such as fission yeast and Dictyostelium [3,5].
• Key to understanding phase separation in cell division.
• Proteomic profiling reveals dynamic changes in microtubule self-organization during M-phase.
• Centrosome-Golgi nexus influences mitotic spindle orientation and organization.
What Happens During microtubule cytoskeleton organization involved in mitosis?
Spindle Assembly and Microtubule Nucleation
In simple terms: The cell builds a tiny machine made of tubes to pull chromosomes apart.
During mitosis, microtubule nucleation is initiated at centrosomes and augmented by chromatin-mediated pathways. The mitotic spindle forms through the assembly of microtubules into a bipolar array that captures chromosomes. Key MAPs such as TPX2 and NuMA promote spindle assembly, while motor proteins like Eg5 (KIF11) crosslink and slide microtubules to establish bipolarity [1,7]. Phase separation of spindle proteins, including TPX2 and BuGZ, contributes to the formation of spindle assembly compartments. In fission yeast, cytoplasmic microtubule organization is regulated by the gamma-tubulin complex and other MAPs.
Kinetochore-Microtubule Attachment
In simple terms: The tubes connect to special handles on chromosomes to pull them.
Kinetochores are protein structures on centromeric chromatin that bind microtubules. The NDC80 complex forms the core attachment site, while the SKA complex and dynein regulate attachment stability and error correction. Aurora B kinase phosphorylates NDC80 to detach incorrect attachments, ensuring bi-orientation. This process is essential for chromosome segregation and is monitored by the spindle assembly checkpoint.
Microtubule Dynamics and Flux
In simple terms: The tubes constantly grow and shrink to position chromosomes correctly.
Mitotic microtubules exhibit dynamic instability, with transitions between growth and shrinkage. Microtubule flux, driven by kinesin-13 motors and poleward movement, contributes to spindle tension and chromosome segregation [1,7]. Proteomic profiling of M-phase microtubule self-organization has identified numerous MAPs that regulate these dynamics.
Spindle Positioning and Orientation
In simple terms: The cell decides where to split by moving the tubes around.
Spindle positioning is regulated by cortical force generators, including dynein and its adaptors. The centrosome-Golgi apparatus nexus influences spindle orientation and asymmetric cell division. In Dictyostelium, nuclear envelope organization is linked to microtubule cytoskeleton dynamics during mitosis.
Spindle Disassembly and Cytokinesis
In simple terms: After chromosomes are separated, the tubes are taken apart.
Following chromosome segregation, the spindle disassembles through microtubule depolymerization and inactivation of mitotic kinases. This process is coordinated with cytokinesis and involves MAPs such as CLASP and kinesin-8 [1,7]. Proper disassembly is required for cell cycle progression and prevents aneuploidy.
Key Genes Involved in GO:1902850 microtubule cytoskeleton organization involved in mitosis
The following genes and proteins are central to microtubule cytoskeleton organization involved in mitosis, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PLK4 | Centriole duplication and centrosome amplification | Target for cancer therapy; inhibition causes mitotic defects |
| TRIM37 | Ubiquitin ligase regulating centrosome homeostasis | Controls cancer-specific vulnerability to PLK4 inhibition |
| NDC80 | Kinetochore-microtubule attachment | Core component of the KMN network; studied for chromosome segregation |
| SKA1 | Kinetochore-microtubule interface | Regulates attachment stability and error correction |
| AURKB | Chromosome bi-orientation and error correction | Phosphorylates NDC80; target for anticancer drugs |
| TPX2 | Spindle assembly and microtubule nucleation | Phase separation in spindle formation |
| KIF11 (Eg5) | Bipolar spindle assembly | Motor protein; target for mitotic inhibitors |
| DYNC1H1 | Dynein heavy chain; spindle positioning | Cortical force generation and spindle orientation |
| NUMA1 | Spindle pole organization | Maintains spindle bipolarity |
| CLASP1 | Microtubule stabilization | Regulates kinetochore-microtubule dynamics |
| KIF2A | Microtubule depolymerization | Kinesin-13 family; regulates flux |
| Gamma-tubulin complex | Microtubule nucleation | Essential for spindle assembly |
| EB1 (MAPRE1) | Microtubule plus-end tracking | Regulates dynamic instability |
| PRC1 | Microtubule bundling in cytokinesis | Central spindle formation |
| Aurora A | Centrosome maturation and spindle assembly | Kinase; target for cancer therapy |
| MAD2 | Spindle assembly checkpoint | Monitors kinetochore-microtubule attachment |
| BUB1 | Spindle checkpoint and chromosome congression | Regulates kinetochore function |
How Is microtubule cytoskeleton organization involved in mitosis Regulated?
The process is regulated by mitotic kinases, including CDK1, Aurora A/B, PLK1, and PLK4, which phosphorylate MAPs and motor proteins to control microtubule dynamics and spindle assembly [1,2,6]. Phosphatases such as PP2A counteract kinase activity to ensure proper spindle disassembly. Phase separation of regulatory proteins, such as BuGZ and TPX2, modulates spindle assembly. Additionally, the ubiquitin-proteasome system, including TRIM37, regulates centrosome homeostasis and mitotic progression.
microtubule cytoskeleton organization involved in mitosis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PLK4 | Cancer (centrosome amplification) | Knockout or overexpression in cancer cell lines |
| TRIM37 | Cancer (PLK4 inhibitor sensitivity) | Knockout in breast cancer cells |
| NDC80 | Aneuploidy and cancer | Point mutation to disrupt microtubule binding |
| DYNC1H1 | Neurodevelopmental disorders | Knock-in of patient mutations in iPSCs |
| AURKB | Cancer and chemoresistance | Overexpression or knockout in HeLa cells |
Cancer and Aneuploidy
Dysregulation of mitotic microtubule organization leads to aneuploidy, a hallmark of cancer. Overexpression of PLK4 causes centrosome amplification, which is observed in breast cancer and other malignancies. TRIM37 loss confers sensitivity to PLK4 inhibition, suggesting a therapeutic strategy for TRIM37-amplified cancers. Targeting kinetochore-microtubule attachment proteins, such as NDC80 and Aurora B, is an active area of anticancer drug development.
Neurodevelopmental Disorders
Mutations in genes regulating mitotic spindle organization, such as those encoding dynein and its adaptors, cause neurodevelopmental disorders including microcephaly and lissencephaly. Proper spindle orientation is critical for neural progenitor cell division and brain development.
Chemoresistance
Alterations in microtubule dynamics and spindle assembly checkpoint proteins contribute to resistance to taxanes and vinca alkaloids. Understanding GO:1902850 mechanisms can inform strategies to overcome chemoresistance.
From microtubule cytoskeleton organization involved in mitosis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does PLK4 overexpression cause centrosome amplification? | Knock-in of PLK4 under inducible promoter |
| What is the role of TRIM37 in PLK4 inhibitor sensitivity? | CRISPR knockout of TRIM37 in cancer cell lines |
| How does NDC80 phosphorylation regulate kinetochore attachment? | Point mutation of Aurora B phosphorylation sites |
| Does dynein mutation affect spindle orientation? | Knock-in of DYNC1H1 mutations in neural progenitors |
| Can phase separation of TPX2 be disrupted? | Overexpression of TPX2 mutants lacking phase separation |
| What is the function of gamma-tubulin in spindle assembly? | Knockout of gamma-tubulin complex components |
How to Study the microtubule cytoskeleton organization involved in mitosis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Spindle dynamics and chromosome segregation | Visualizing mitotic defects in real time [1,6] |
| Proteomics | Protein composition of mitotic spindles | Identifying novel MAPs and modifications |
| CRISPR knockout screening | Gene essentiality for mitosis | Discovering therapeutic targets |
| In vitro reconstitution | Microtubule dynamics and motor activity | Mechanistic studies of MAPs |
| Phosphoproteomics | Kinase substrate identification | Mapping mitotic phosphorylation networks |
| RNA-seq | Transcriptional changes during mitosis | Identifying gene expression programs |
| Super-resolution microscopy | Nanoscale architecture of kinetochores | Studying attachment sites |
| Yeast genetics | Conserved mitotic mechanisms | Modeling microtubule organization |
Live-Cell Imaging
Fluorescently tagged tubulin and MAPs enable real-time visualization of spindle assembly and chromosome segregation. This method reveals dynamic defects in microtubule organization [1,6].
Proteomic Profiling
Mass spectrometry-based proteomics of isolated mitotic spindles identifies MAPs and their post-translational modifications, providing a systems-level view of microtubule self-organization.
CRISPR Screening
Genome-wide CRISPR knockout screens can identify genes required for mitotic microtubule organization and chromosome segregation, as demonstrated for PLK4 inhibitor sensitivity.
In Vitro Reconstitution
Purified tubulin and MAPs can be reconstituted to study microtubule nucleation, dynamics, and crosslinking in vitro, revealing intrinsic mechanisms.
How CRISPR Can Be Used to Study GO:1902850 microtubule cytoskeleton organization involved in mitosis
Knockout
CRISPR knockout of genes such as TRIM37 or PLK4 in cancer cell lines has revealed their roles in centrosome homeostasis and mitotic vulnerability. Knockout of kinetochore components like NDC80 causes chromosome segregation defects.
Point Mutation
Point mutations can be introduced to disrupt specific phosphorylation sites or protein-protein interaction domains, such as in NDC80 to study Aurora B regulation. This approach dissects molecular mechanisms without altering protein levels.
Knock-in
Knock-in of fluorescent tags or disease-associated mutations allows visualization and functional analysis of mitotic proteins. For example, knock-in of DYNC1H1 mutations in iPSCs models neurodevelopmental disorders.
Overexpression
Overexpression of PLK4 or TPX2 induces centrosome amplification and spindle defects, providing models for cancer and phase separation studies [2,4].
How EDITGENE Supports microtubule cytoskeleton organization involved in mitosis Research
Researchers studying microtubule cytoskeleton organization involved in mitosis-related genes often need to determine whether a candidate gene is causally involved in spindle assembly, kinetochore attachment, or chromosome segregation. EDITGENE provides a comprehensive suite of CRISPR services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for microtubule cytoskeleton organization involved in mitosis research.
Frequently Asked Questions About microtubule cytoskeleton organization involved in mitosis
What is GO:1902850?
GO:1902850 is a Gene Ontology biological process term defined as any microtubule cytoskeleton organization that is involved in mitosis, including spindle assembly and kinetochore-microtubule attachment [1,6].
What genes are involved in microtubule cytoskeleton organization involved in mitosis?
Key genes include PLK4, TRIM37, NDC80, SKA1, AURKB, TPX2, KIF11, DYNC1H1, and NUMA1, among others [1,2,6].
Why is microtubule cytoskeleton organization important for mitosis?
It ensures accurate chromosome segregation and genomic stability; defects lead to aneuploidy and cancer [2,6].
How is microtubule cytoskeleton organization involved in mitosis regulated?
It is regulated by mitotic kinases (CDK1, Aurora A/B, PLK1/4), phosphatases, and phase separation of spindle proteins [1,2,4].
What diseases are associated with defects in mitotic microtubule organization?
Cancer, neurodevelopmental disorders such as microcephaly, and chemoresistance [2,8].
What methods are used to study GO:1902850?
Live-cell imaging, proteomics, CRISPR screens, and in vitro reconstitution are commonly used [1,6,7].
Can CRISPR be used to study mitotic microtubule organization?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools for dissecting gene function in mitosis [2,6].
What is the role of phase separation in mitotic microtubule organization?
Phase separation of proteins like TPX2 and BuGZ contributes to spindle assembly and organization.
How does PLK4 relate to microtubule cytoskeleton organization?
PLK4 regulates centriole duplication and centrosome amplification, which are critical for mitotic spindle formation.
What is the kinetochore-microtubule interface?
It is the connection between kinetochores and spindle microtubules, mediated by NDC80 and SKA complexes, essential for chromosome segregation.
Conclusion
GO:1902850 encompasses the essential microtubule organization events that drive mitosis, from spindle assembly to kinetochore attachment and disassembly. Understanding its molecular players and regulation is crucial for cancer biology, neurodevelopment, and therapeutic development [1,2,6]. EDITGENE provides advanced CRISPR tools to study these processes and accelerate discovery.
References
- 1. Goodson HV et al.. 2018. Microtubules and Microtubule-Associated Proteins.. Cold Spring Harb Perspect Biol 10(6) PMID: 29858272
- 2. Meitinger F et al.. 2020. TRIM37 controls cancer-specific vulnerability to PLK4 inhibition.. Nature 585(7825):440-446 PMID: 32908304
- 3. Sawin KE et al.. 2006. Cytoplasmic microtubule organization in fission yeast.. Yeast 23(13):1001-14 PMID: 17072892
- 4. Ong JY et al.. 2020. Phase Separation in Cell Division.. Mol Cell 80(1):9-20 PMID: 32860741
- 5. Batsios P et al.. 2019. Nuclear envelope organization in Dictyostelium discoideum.. Int J Dev Biol 63(8-9-10):509-519 PMID: 31840788
- 6. Monda JK et al.. 2018. The kinetochore-microtubule interface at a glance.. J Cell Sci 131(16) PMID: 30115751
- 7. Rosas-Salvans M et al.. 2018. Proteomic Profiling of Microtubule Self-organization in M-phase.. Mol Cell Proteomics 17(10):1991-2004 PMID: 29970457
- 8. Rios RM. 2014. The centrosome-Golgi apparatus nexus.. Philos Trans R Soc Lond B Biol Sci 369(1650) PMID: 25047616
