GO:0150101 regulation of microtubule anchoring at centrosome: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0150101 describes any process that modulates the frequency, rate or extent of microtubule anchoring at the centrosome, a critical step for cell polarity, spindle orientation and ciliogenesis [2, 7].
• The centrosome acts as the primary microtubule-organizing center (MTOC) in animal cells, and its ability to anchor microtubule minus ends is dynamically regulated during the cell cycle and differentiation [7, 8].
• Key proteins involved include centriolar satellite components, pericentriolar material (PCM) proteins such as CDK5RAP2 and pericentrin, and motor proteins like dynein that transport and tether microtubules [1, 7].
• Dysregulation of microtubule anchoring is linked to neurodevelopmental disorders, ciliopathies, skeletal muscle diseases and cancer [1, 3, 4].
• CRISPR-based knockout, knock-in and overexpression models are essential to dissect the causal roles of specific genes in microtubule anchoring at the centrosome [1, 6].
• Advanced imaging, proteomics and functional assays combined with CRISPR screening provide a robust toolkit to study this process in health and disease [1, 5].
Description
The centrosome is the major microtubule-organizing center in animal cells, and its ability to anchor microtubule minus ends is fundamental for establishing cell polarity, orienting the mitotic spindle and nucleating cilia [2, 7]. The Gene Ontology term GO:0150101, regulation of microtubule anchoring at centrosome, encompasses any process that modulates the frequency, rate or extent of microtubule anchoring at the centrosome. This regulatory process ensures that microtubules are properly tethered to the centrosome, which is essential for asymmetric cell division, cell migration and tissue morphogenesis [2, 8]. Research over the past two decades has revealed that microtubule anchoring is not a static event but is dynamically controlled by a complex network of centrosomal and pericentriolar material (PCM) proteins, motor proteins and post-translational modifications [1, 7]. For example, the spatial centrosome proteome of human neural cells has uncovered disease-relevant heterogeneity in centrosomal protein composition, highlighting the importance of context-dependent regulation. Moreover, defects in microtubule anchoring contribute to a spectrum of human disorders, including ciliopathies, neurodevelopmental defects and skeletal muscle diseases [3, 4]. Understanding GO:0150101 is therefore critical for researchers studying cell biology, developmental biology and disease mechanisms. This article provides a comprehensive overview of the definition, molecular players, regulatory mechanisms, disease associations and experimental approaches, with a focus on how CRISPR-based models can accelerate discovery in this field.
regulation of microtubule anchoring at centrosome At A Glance
| GO ID | GO:0150101 |
|---|---|
| GO term | regulation of microtubule anchoring at centrosome |
| Ontology | biological_process |
| Synonym | None |
| Major function | Modulates the anchoring of microtubule minus ends at the centrosome, influencing cell polarity, spindle orientation and ciliogenesis [2, 7] |
| Related cellular component | Centrosome, pericentriolar material (PCM), centriolar satellites [1, 7] |
| Key molecular players | CDK5RAP2, pericentrin (PCNT), dynein, dynactin, ninein, CEP proteins [1, 7] |
| Associated diseases | Ciliopathies, neurodevelopmental disorders, skeletal muscle diseases, cancer [1, 3, 4] |
| Research methods | CRISPR knockout/knock-in, live-cell imaging, proteomics, RNA-seq [1, 5, 6] |
What Is GO:0150101?
GO:0150101, regulation of microtubule anchoring at centrosome, is defined as any process that modulates the frequency, rate or extent of microtubule anchoring at centrosome. In other words, it covers the cellular mechanisms that control how microtubule minus ends are attached or tethered to the centrosome, ensuring proper microtubule organization and function [7, 8].
Why Is regulation of microtubule anchoring at centrosome Important in Cell Biology?
Regulation of microtubule anchoring at the centrosome is fundamental to many cellular processes, including cell division, migration, polarization and primary cilia formation [2, 7]. Disruption of this regulation leads to defects in spindle orientation, chromosome segregation errors and impaired signaling, which are associated with developmental disorders and cancer [1, 4]. Therefore, understanding GO:0150101 provides insights into basic cell biology and human disease mechanisms.
• Ensures proper spindle orientation and asymmetric cell division during development.
• Required for cell polarity and directed migration in epithelial and neural cells.
• Essential for ciliogenesis and ciliary function, with links to ciliopathies [3, 6].
• Involved in skeletal muscle maintenance and disease.
• Dysregulation contributes to neurodevelopmental disorders such as microcephaly.
• Altered microtubule anchoring is observed in various cancers, affecting mitosis and invasion.
• Provides targets for therapeutic intervention in centrosome-related diseases.
• Serves as a model for studying organelle positioning and cytoskeletal dynamics.
• Key to understanding the spatial organization of signaling pathways.
• Facilitates the development of CRISPR-based disease models.
What Happens During regulation of microtubule anchoring at centrosome?
Centrosome Maturation and PCM Assembly
In simple terms: The centrosome gets ready by building a protein scaffold that will hold microtubules.
Before microtubules can be anchored, the centrosome must mature and assemble a pericentriolar material (PCM) that contains anchoring proteins such as CDK5RAP2 and pericentrin. This process is regulated by cell cycle kinases and is essential for creating a docking site for microtubule minus ends.
Microtubule Nucleation and Minus-End Tethering
In simple terms: New microtubules are born at the centrosome and their back ends are tied down.
Microtubule nucleation is initiated by the gamma-tubulin ring complex (gamma-TuRC) at the centrosome, and the minus ends of newly formed microtubules are anchored to PCM components. Proteins like ninein and CEP proteins facilitate the tethering, ensuring that microtubules remain attached.
Motor-Protein Dependent Transport and Anchoring
In simple terms: Molecular motors help pull microtubules into place and secure them.
Dynein and dynactin are recruited to the centrosome and help transport and anchor microtubules by interacting with PCM proteins. This motor-dependent mechanism is crucial for maintaining microtubule organization and for dynamic rearrangements during cell cycle progression.
Dynamic Regulation by Post-Translational Modifications
In simple terms: Chemical tags on proteins can loosen or tighten the anchoring.
Phosphorylation, acetylation and other post-translational modifications of centrosomal proteins regulate the strength and dynamics of microtubule anchoring [1, 6]. For example, phosphorylation of CDK5RAP2 by CDK1 during mitosis promotes PCM expansion and increased anchoring capacity.
Anchoring at the Mother Centriole and Distal Appendages
In simple terms: The older centriole has special structures that help anchor microtubules and cilia.
The mother centriole possesses distal and subdistal appendages that are involved in microtubule anchoring and ciliogenesis. Proteins such as ODF2 and CEP164 localize to these appendages and regulate the anchoring of microtubules and the assembly of primary cilia.
Key Genes Involved in GO:0150101 regulation of microtubule anchoring at centrosome
The following genes and proteins are key players in the regulation of microtubule anchoring at the centrosome, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CDK5RAP2 | PCM scaffold protein, regulates gamma-TuRC anchoring | Mutations cause microcephaly; target for CRISPR KO |
| PCNT | Pericentrin, major PCM component, anchors microtubules | Dysregulated in dwarfism and cancer; model for knock-in |
| DYNCH1 | Dynein heavy chain, motor for microtubule anchoring | Mutations linked to neurodevelopmental disorders |
| NIN | Ninein, anchors microtubule minus ends at centrosome | Key for epithelial polarity; KO models available |
| CEP164 | Distal appendage protein, involved in ciliogenesis | Ciliopathy-related; CRISPR KO models |
| ODF2 | Outer dense fiber protein 2, centriole appendage component | Required for anchoring and cilia formation |
| CEP152 | Centrosomal protein, regulates PCM assembly | Mutations cause Seckel syndrome; KO models |
| STIL | Centriolar satellite protein, regulates centriole duplication | Linked to microcephaly; CRISPR studies |
| SASS6 | Centriole assembly factor | Essential for centrosome integrity; KO models |
| PLK1 | Kinase regulating centrosome maturation | Phosphorylates PCM proteins; inhibitor studies |
| AURKA | Kinase promoting centrosome maturation | Overexpression in cancer; target for KO |
| TUBG1 | Gamma-tubulin, core of gamma-TuRC | Nucleates microtubules; point mutations in disease |
| TUBGCP2 | Gamma-TuRC component | Regulates nucleation and anchoring |
| DCTN1 | Dynactin subunit, cofactor for dynein | Mutations in motor neuron disease; KO models |
| B9D1 | B9 protein complex, ciliary microtubule regulation | Ciliopathy-related; CRISPR KO |
| B9D2 | B9 protein complex, ciliary microtubule regulation | Ciliopathy-related; CRISPR KO |
| CC2D2A | Centrosomal protein, ciliogenesis regulator | Mutations in Joubert syndrome; KO models |
How Is regulation of microtubule anchoring at centrosome Regulated?
The regulation of microtubule anchoring at the centrosome is controlled by multiple signaling pathways and cell cycle regulators. CDK1-cyclin B and PLK1 kinases promote centrosome maturation and PCM expansion during mitosis, enhancing microtubule anchoring capacity. Aurora A kinase also contributes to PCM assembly and anchoring. Conversely, phosphatases such as PP2A counteract these phosphorylation events to ensure proper timing. Additionally, the spatial centrosome proteome is dynamically regulated during neural differentiation, with changes in protein composition affecting anchoring efficiency. Post-translational modifications, including acetylation and polyglutamylation of tubulin, also modulate anchoring stability.
regulation of microtubule anchoring at centrosome and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CDK5RAP2 | Microcephaly, neurodevelopmental defects | CRISPR KO in neural stem cells |
| CEP164 | Ciliopathies (Joubert, Meckel) | Knock-in of patient mutations in RPE1 cells |
| PCNT | Microcephalic osteodysplastic primordial dwarfism | Point mutation knock-in in HEK293T |
| B9D1 | Ciliopathies (Meckel syndrome) | KO in human fibroblasts |
| AURKA | Cancer (overexpression) | Overexpression in cancer cell lines |
Neurodevelopmental Disorders
Mutations in centrosomal genes such as CDK5RAP2, CEP152 and STIL cause microcephaly and Seckel syndrome by impairing microtubule anchoring and spindle orientation in neural progenitors. The spatial centrosome proteome of human neural cells has revealed disease-relevant heterogeneity, underscoring the importance of proper anchoring for brain development.
Ciliopathies
Defects in microtubule anchoring at the mother centriole disrupt ciliogenesis, leading to ciliopathies such as Joubert syndrome and Meckel syndrome [3, 6]. Proteins like CEP164, ODF2 and B9 complex components are critical for anchoring and ciliary assembly, and their dysfunction results in multisystem disorders [3, 6].
Skeletal Muscle Diseases
Centrosome and microtubule anchoring defects contribute to skeletal muscle pathologies, including muscular dystrophies and myopathies. Proper microtubule organization is essential for muscle fiber formation and maintenance, and disruption leads to impaired regeneration.
Cancer
Altered microtubule anchoring can cause mitotic spindle defects, chromosomal instability and invasive migration, promoting tumorigenesis. Overexpression of AURKA and PLK1, which enhance anchoring, is observed in many cancers and is a therapeutic target.
From regulation of microtubule anchoring at centrosome-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of CDK5RAP2 affect microtubule anchoring? | CRISPR KO in human neural progenitors |
| How do point mutations in CEP164 alter ciliogenesis? | CRISPR knock-in of patient mutations in RPE1 |
| Can overexpression of AURKA drive centrosome amplification? | CRISPR overexpression in HeLa cells |
| What is the interactome of pericentrin at the centrosome? | Endogenous knock-in of GFP-PCNT |
| Does dynactin mutation impair dynein-mediated anchoring? | CRISPR KO of DCTN1 in motor neurons |
| How does B9D1 mutation affect ciliary microtubule modifications? | CRISPR KO in human fibroblasts |
How to Study the regulation of microtubule anchoring at centrosome Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Microtubule dynamics and anchoring | Real-time analysis of centrosome function |
| Proximity labeling proteomics | Centrosome protein composition | Identifying novel anchoring regulators |
| CRISPR knockout screening | Gene essentiality for anchoring | Discovery of new pathway components |
| Super-resolution microscopy | Nanoscale structure of anchoring sites | Visualizing appendage defects |
| RNA-seq | Transcriptional changes upon perturbation | Assessing downstream effects |
| Co-immunoprecipitation | Protein-protein interactions | Validating anchoring complex components |
| Electron microscopy | Ultrastructure of centrioles and microtubules | Detecting structural abnormalities |
Live-Cell Imaging of Microtubule Dynamics
Fluorescently labeled tubulin and centrosomal markers allow real-time visualization of microtubule anchoring and release. This method reveals dynamic changes during cell cycle and in response to perturbations [7, 8].
Proteomic Profiling of the Centrosome
Spatial proteomics using proximity labeling or affinity purification coupled to mass spectrometry identifies the composition of the centrosome and its changes under different conditions. This approach has uncovered disease-relevant heterogeneity in neural cells.
CRISPR-Based Functional Genomics
Genome-wide CRISPR knockout or activation screens can identify genes that regulate microtubule anchoring. These screens are powerful for discovering novel regulators and validating candidate genes [1, 6].
Electron Microscopy and Super-Resolution Imaging
Ultrastructural analysis by electron microscopy and super-resolution microscopy (e.g., STORM, STED) provides detailed views of centriole appendages and microtubule attachment sites, revealing structural defects in mutants.
How CRISPR Can Be Used to Study GO:0150101 regulation of microtubule anchoring at centrosome
Knockout
CRISPR knockout of genes such as CDK5RAP2, CEP164 or DCTN1 in cell lines or primary cells allows researchers to assess their requirement for microtubule anchoring. Knockout models have revealed essential roles in centrosome integrity and ciliogenesis [1, 6].
Point Mutation
Introducing patient-specific point mutations (e.g., in PCNT or CEP164) via CRISPR knock-in recapitulates disease-associated defects in microtubule anchoring, enabling mechanistic studies and drug testing [6, 7].
Knock-in
Tagging endogenous anchoring proteins with fluorescent or affinity tags (e.g., GFP-PCNT) using CRISPR knock-in allows real-time tracking and interactome analysis without overexpression artifacts.
Overexpression
CRISPR-mediated overexpression of genes like AURKA or PLK1 can mimic cancer-associated states and test sufficiency for centrosome amplification and altered anchoring.
How EDITGENE Supports regulation of microtubule anchoring at centrosome Research
Researchers studying regulation of microtubule anchoring at centrosome-related genes often need to determine whether a candidate gene is causally involved in the process, and CRISPR-based models provide the most direct approach. EDITGENE offers a comprehensive suite of services to generate and characterize such models.
Contact EDITGENE today to design your custom CRISPR model for regulation of microtubule anchoring at centrosome research.
Frequently Asked Questions About regulation of microtubule anchoring at centrosome
What is GO:0150101?
GO:0150101 is a Gene Ontology term for regulation of microtubule anchoring at centrosome, describing any process that modulates the frequency, rate or extent of microtubule anchoring at the centrosome.
What genes are involved in regulation of microtubule anchoring at centrosome?
Key genes include CDK5RAP2, PCNT, DYNCH1, NIN, CEP164, ODF2, CEP152, STIL, SASS6, PLK1, AURKA, TUBG1, TUBGCP2, DCTN1, B9D1, B9D2 and CC2D2A [1, 3, 6, 7].
Why is microtubule anchoring at the centrosome important?
It is essential for cell polarity, spindle orientation, ciliogenesis and tissue development; defects cause neurodevelopmental disorders, ciliopathies and cancer [1, 3, 4].
How is microtubule anchoring regulated?
It is regulated by cell cycle kinases (CDK1, PLK1, AURKA), phosphatases, post-translational modifications and dynamic changes in centrosome composition [1, 7].
What diseases are linked to defective microtubule anchoring?
Microcephaly, Seckel syndrome, Joubert syndrome, Meckel syndrome, skeletal muscle diseases and cancer [1, 3, 4, 7].
What methods are used to study microtubule anchoring?
Live-cell imaging, proteomics, CRISPR screening, super-resolution microscopy, RNA-seq and co-immunoprecipitation [1, 5, 6, 7].
Can CRISPR be used to study microtubule anchoring?
Yes, CRISPR knockout, knock-in and overexpression models are widely used to dissect gene function in this process [1, 6, 7].
What is the role of the centrosome in microtubule anchoring?
The centrosome serves as the main microtubule-organizing center, and its PCM and appendages anchor microtubule minus ends [7, 8].
How does ciliogenesis relate to microtubule anchoring?
Proper anchoring at the mother centriole is required for ciliary axoneme formation; defects lead to ciliopathies [3, 6].
What cell models are available for studying GO:0150101?
Common models include RPE1, HEK293T, neural progenitors, fibroblasts and cancer cell lines, often engineered with CRISPR [1, 6, 7].
Conclusion
Regulation of microtubule anchoring at the centrosome (GO:0150101) is a fundamental biological process that ensures proper cytoskeletal organization, cell polarity and division. Its dysregulation underlies a range of human diseases, from neurodevelopmental disorders to cancer. Continued research using advanced CRISPR models and imaging techniques will further elucidate the molecular mechanisms and identify therapeutic targets. EDITGENE provides the tools and expertise to accelerate these discoveries.
References
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- 2. Meiring JCM et al.. 2020. Generation and regulation of microtubule network asymmetry to drive cell polarity.. Curr Opin Cell Biol 62:86-95 PMID: 31739264
- 3. He R et al.. 2026. Ciliopathy-related B9 protein complex regulates ciliary axonemal microtubule posttranslational modifications and initiation of ciliogenesis.. J Clin Invest 136(2) PMID: 41165761
- 4. Ng DCH et al.. 2021. Cilia, Centrosomes and Skeletal Muscle.. Int J Mol Sci 22(17) PMID: 34502512
- 5. Vasileva E et al.. 2018. The role of microtubules in the regulation of epithelial junctions.. Tissue Barriers 6(3):1539596 PMID: 30395792
- 6. Je SY et al.. 2024. Distinct roles of centriole distal appendage proteins in ciliary assembly and disassembly.. Cell Commun Signal 22(1):607 PMID: 39696441
- 7. Gavilan MP et al.. 2018. The dual role of the centrosome in organizing the microtubule network in interphase.. EMBO Rep 19(11) PMID: 30224411
- 8. Dammermann A et al.. 2003. The minus end in sight.. Curr Biol 13(15):R614-24 PMID: 12906817
