GO:1903754 cortical microtubule plus-end: Components, Assembly and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1903754 (cortical microtubule plus-end) is a cellular component defined as the plus-end of a cortical microtubule, the dynamic growing end that faces the cell cortex.
• Plus-end tracking proteins (+TIPs) such as ARK2, Gcap14, SLAIN1/2, ch-TOG and Tao-1 bind this region to control microtubule growth, bundling and cortical attachment.
• The cortical microtubule plus-end is a hub for microtubule-actin crosstalk, exocytosis and cell morphogenesis, especially in neurons and plant cells.
• Dysregulation of plus-end dynamics is linked to neurodevelopmental defects, axon outgrowth failure and mitotic errors.
• CRISPR knockout, point mutation, knock-in and overexpression models are essential to dissect plus-end protein function in vivo.
• Live-cell imaging of fluorescently labeled +TIPs combined with CRISPR editing provides the most direct readout of cortical microtubule plus-end behavior.
Description
The cortical microtubule plus-end (GO:1903754) is the growing end of a microtubule that is anchored or positioned near the cell cortex, the inner face of the plasma membrane. In plant cells, cortical microtubules form ordered arrays that guide cellulose deposition and cell elongation, and their plus-ends are the sites where new tubulin dimers are added and where regulatory proteins accumulate. In animal cells, cortical microtubule plus-ends are critical for attaching the microtubule cytoskeleton to the cortex, for polarized exocytosis and for neuronal development. Because this structure is the primary interface between the microtubule network and the cell periphery, it is a focal point for understanding how cells organize their shape and respond to external cues. Researchers study GO:1903754 to identify the proteins that track plus-ends, to measure microtubule dynamics in living cells and to link plus-end dysfunction to disease. The term is therefore central to cell biology, neurobiology and plant developmental biology.
cortical microtubule plus-end At A Glance
| GO ID | GO:1903754 |
|---|---|
| GO term | cortical microtubule plus-end |
| Ontology | cellular_component |
| Synonym | cortical microtubule plus end |
| Major function | Dynamic growing end of cortical microtubules; platform for +TIP binding and microtubule-cortex interactions |
| Related process | Microtubule polymerization, cortical attachment, exocytosis, cell morphogenesis |
| Key proteins | ARK2, Gcap14, SLAIN1/2, ch-TOG, Tao-1, CLIP-170, EB1 |
| Research methods | Live-cell imaging of fluorescent +TIPs, CRISPR knockout/knock-in, microtubule polymerization assays |
What Is GO:1903754?
According to the Gene Ontology, GO:1903754 (cortical microtubule plus-end) is the plus-end of a cortical microtubule. A cortical microtubule is a microtubule located near the cell cortex, and its plus-end is the dynamic end where tubulin polymerization occurs. This cellular component is defined by its subcellular location and its role as a docking site for plus-end tracking proteins (+TIPs) that regulate microtubule growth, shrinkage and interactions with the cortex.
Why Is cortical microtubule plus-end Important in Cell Biology?
The cortical microtubule plus-end is important because it is the primary site where microtubule dynamics are coupled to the cell cortex, influencing cell shape, division and differentiation. In plants, cortical microtubule plus-ends guide the deposition of cellulose microfibrils, which determines anisotropic cell growth. In animals, plus-end tracking proteins at the cortex are required for axon outgrowth, neuronal migration and polarized exocytosis. Defects in plus-end regulation can lead to mitotic spindle misorientation, neurodevelopmental disorders and impaired tissue morphogenesis. Therefore, understanding GO:1903754 provides mechanistic insight into fundamental cell biology and candidate therapeutic targets.
• Controls directional cell growth in plants by guiding cellulose synthase complexes at the cortex.
• Regulates axon outgrowth and neuronal development through +TIPs such as SLAIN1/2 and ch-TOG.
• Coordinates microtubule-actin crosstalk during neurodevelopment via Gcap14.
• Required for proper anaphase B spindle elongation and chromosome segregation.
• Facilitates cortical exocytosis and membrane trafficking.
• Dysregulation is linked to neurodevelopmental defects and mitotic errors.
• Serves as a target for herbicides and potential cancer therapeutics.
• Provides a model for studying cytoskeletal self-organization.
• Enables live-cell analysis of microtubule dynamics using fluorescent +TIPs.
• Offers a platform for CRISPR-based functional genomics of plus-end proteins.
What Happens During cortical microtubule plus-end?
Microtubule polymerization at the plus-end
In simple terms: New tubulin building blocks are added to the growing end of the microtubule.
The cortical microtubule plus-end is the site of tubulin dimer addition, which drives microtubule elongation. This polymerization is regulated by plus-end tracking proteins that either promote or inhibit growth. For example, ARK2 stabilizes the plus-end and promotes microtubule bundling in Arabidopsis. Tao-1 acts as a negative regulator of plus-end growth, limiting microtubule extension. The balance between promoting and inhibiting factors determines the overall dynamics of the cortical array.
Plus-end tracking protein (+TIP) binding
In simple terms: Special proteins recognize and bind to the growing end to control its behavior.
A diverse set of +TIPs, including Gcap14, SLAIN1/2, ch-TOG, CLIP-170 and EB1, specifically accumulate at microtubule plus-ends. These proteins form a dynamic network that links the plus-end to cellular structures such as the actin cortex and exocytic vesicles. Gcap14 coordinates microtubule-actin crosstalk during neurodevelopment, while SLAIN1/2 and ch-TOG promote axonal development. Their binding is often mediated by recognition of the microtubule lattice or by mutual interactions.
Cortical attachment and exocytosis
In simple terms: The growing end connects to the cell edge and helps deliver materials to the membrane.
Cortical microtubule plus-ends interact with the cell cortex through linker proteins, enabling the microtubule network to sense and respond to cortical cues. This attachment is coupled to exocytosis, as plus-end proteins help target secretory vesicles to specific cortical domains. In plant cells, this interaction guides the deposition of cell wall materials. Disruption of cortical attachment leads to disorganized microtubule arrays and defective cell morphogenesis.
Microtubule bundling and array organization
In simple terms: Plus-end proteins help group microtubules into bundles for coordinated growth.
Proteins such as ARK2 not only stabilize plus-ends but also promote microtubule bundling, which is essential for forming ordered cortical arrays. Bundling allows neighboring microtubules to align and coordinate their growth, contributing to anisotropic cell expansion. This organization is dynamic and can be remodeled in response to developmental or environmental signals.
Regulation by kinases and signaling
In simple terms: Enzymes can add chemical tags to plus-end proteins to turn their activity up or down.
The activity of plus-end proteins is regulated by phosphorylation and other post-translational modifications. Tao-1 is a kinase that negatively regulates plus-end growth, likely by phosphorylating components at the plus-end. Other signaling pathways, such as those involving Rho GTPases, may also influence plus-end dynamics, although the exact mechanisms remain to be fully defined. This regulation ensures that microtubule growth is coordinated with cell cycle progression and developmental cues.
Key Genes Involved in GO:1903754 cortical microtubule plus-end
The following genes and proteins are experimentally implicated in the structure, regulation or function of the cortical microtubule plus-end (GO:1903754).
| Gene | Major Role | Research Relevance |
|---|---|---|
| ARK2 | Stabilizes plus-end and promotes microtubule bundling in Arabidopsis | Plant cell morphogenesis; herbicide target |
| Gcap14 | Microtubule plus-end-tracking protein coordinating microtubule-actin crosstalk | Neurodevelopment; axon guidance |
| SLAIN1 | Plus-end tracking protein promoting axonal development | Neuronal differentiation; axon outgrowth |
| SLAIN2 | Plus-end tracking protein promoting axonal development | Neuronal differentiation; axon outgrowth |
| ch-TOG | Plus-end tracking protein promoting axonal development | Microtubule polymerization; axon outgrowth |
| Tao-1 | Negative regulator of microtubule plus-end growth | Microtubule dynamics; kinase signaling |
| CLIP-170 | Plus-end tracking protein linking microtubules to cortex | Cortical attachment; cell polarity |
| EB1 | Core plus-end tracking protein | Microtubule dynamics; cell migration |
| DdCP224 | Centrosomal plus-end tracking protein in Dictyostelium | Cell dynamics; chemotaxis |
| DdEB1 | Plus-end tracking protein in Dictyostelium | Cell dynamics; chemotaxis |
| XMAP215 | Microtubule polymerase | Microtubule growth regulation |
| CLASP | Microtubule plus-end tracking protein | Cortical attachment; spindle positioning |
| Kinesin-13 | Microtubule depolymerase | Plus-end dynamics; mitotic spindle |
| Kinesin-5 | Motor protein crosslinking microtubules | Anaphase B spindle elongation |
| Kinesin-4 | Motor protein regulating microtubule length | Cortical array organization |
| MAP65 | Microtubule bundling protein | Cortical microtubule organization |
| Rho GTPase | Signaling protein regulating cortical attachment | Exocytosis; cell polarity |
| Exocyst complex | Tethering complex for exocytosis | Cortical exocytosis; plus-end coupling |
How Is cortical microtubule plus-end Regulated?
The cortical microtubule plus-end is regulated by a combination of plus-end tracking proteins, kinases and signaling pathways. Tao-1 kinase negatively regulates plus-end growth, likely through phosphorylation of plus-end components. ARK2 stabilizes the plus-end and promotes bundling, counteracting depolymerization. In animal cells, Rho GTPase signaling and the exocyst complex coordinate plus-end attachment to the cortex and exocytosis. During mitosis, kinesin motors and other spindle proteins regulate plus-end dynamics to ensure proper anaphase B spindle elongation. These regulatory layers allow the cell to fine-tune microtubule growth in response to developmental and environmental cues.
cortical microtubule plus-end and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Gcap14 | Neurodevelopmental disorders | Knockout mouse or human iPSC-derived neurons |
| SLAIN1/2 | Axon outgrowth defects | CRISPR knockout in primary neurons |
| ch-TOG | Neurodegeneration | Knock-in of patient mutations in neuronal cells |
| Tao-1 | Cancer (mitotic errors) | Knockout in cancer cell lines |
| ARK2 | Plant growth defects | Arabidopsis knockout and overexpression |
Neurodevelopmental disorders
Proper regulation of cortical microtubule plus-ends is essential for neuronal development. Gcap14 coordinates microtubule-actin crosstalk during neurodevelopment, and its dysfunction may contribute to neurodevelopmental disorders. SLAIN1/2 and ch-TOG promote axonal development, and their depletion impairs axon outgrowth, a hallmark of certain neuropathies. These findings suggest that plus-end proteins are candidate genes for neurodevelopmental conditions.
Cancer and mitotic errors
Accurate chromosome segregation during mitosis depends on proper microtubule plus-end dynamics. Kinesin-5 and other motors regulate anaphase B spindle elongation, and their perturbation can lead to aneuploidy, a common feature of cancer cells. Tao-1, a negative regulator of plus-end growth, may influence mitotic spindle assembly and genomic stability. Thus, plus-end regulators are potential targets for anticancer therapies.
Plant development and crop traits
In plants, cortical microtubule plus-ends guide cellulose deposition and anisotropic growth. ARK2 stabilizes plus-ends and promotes bundling, affecting cell elongation and plant architecture. Mutations in plus-end regulators can alter plant morphology, making them relevant for crop improvement.
From cortical microtubule plus-end-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of Gcap14 impair neuronal migration? | Gcap14 knockout mouse or iPSC-derived neurons |
| How does ARK2 mutation affect microtubule bundling? | ARK2 point-mutation knock-in in Arabidopsis |
| Can Tao-1 overexpression suppress tumor growth? | Tao-1 overexpression in cancer cell lines |
| What is the dynamic behavior of SLAIN2 at plus-ends? | SLAIN2 tagged knock-in with fluorescent protein |
| Does ch-TOG mutation alter axon outgrowth? | ch-TOG knockout in primary neurons |
| How does cortical attachment regulate exocytosis? | Knockout of exocyst components in epithelial cells |
How to Study the cortical microtubule plus-end Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell TIRF microscopy | Plus-end growth and shrinkage dynamics | Neuronal and plant cells |
| In vitro polymerization assay | Microtubule elongation rate | Recombinant +TIPs |
| CRISPR knockout screen | Gene requirement for plus-end function | Cancer and neuronal cell lines |
| Proximity ligation assay | Protein-protein interactions at plus-ends | Fixed cells |
| Mass spectrometry | Plus-end complex composition | Biochemical purification |
| Fluorescence recovery after photobleaching | Turnover of +TIPs at plus-ends | Live cells |
| Electron microscopy | Ultrastructure of cortical microtubules | Plant and animal tissues |
| Genetic epistasis | Order of gene action | Arabidopsis and Drosophila |
Live-cell imaging of fluorescent +TIPs
Fluorescently labeled microtubule plus-end tracking proteins, such as EB1-GFP or CLIP-170-GFP, allow real-time visualization of plus-end dynamics in living cells. This method measures growth rate, shrinkage frequency and pause duration at the cortex. It is widely used in neuronal and plant cells to study cortical microtubule plus-end behavior.
Microtubule polymerization assays
In vitro microtubule polymerization assays using purified tubulin and recombinant plus-end proteins can quantify the effect of specific proteins on polymerization rates. For example, ARK2 stabilizes plus-ends and promotes bundling in such assays. Tao-1 has been shown to negatively regulate plus-end growth in vitro.
CRISPR-based functional genomics
CRISPR knockout screens can identify genes required for cortical microtubule plus-end function. Libraries targeting +TIPs and related genes can be introduced into cells, followed by imaging-based or fitness-based readouts. This approach has been used to uncover roles for Gcap14, SLAIN1/2 and ch-TOG in neurodevelopment.
Proteomics of plus-end complexes
Biochemical isolation of plus-end tracking protein complexes followed by mass spectrometry can identify novel interactors and post-translational modifications. This method has been applied to Dictyostelium plus-end proteins to map their interaction network.
How CRISPR Can Be Used to Study GO:1903754 cortical microtubule plus-end
Knockout
CRISPR knockout of plus-end genes such as Gcap14, SLAIN1/2 or ch-TOG can reveal their essential roles in neuronal development and microtubule dynamics. Knockout cell lines and animal models are used to assess loss-of-function phenotypes, including axon outgrowth defects and mitotic errors.
Point Mutation
Point mutations in plus-end genes can mimic disease-associated variants or disrupt specific protein interactions. For example, point mutations in ARK2 can be introduced to test its role in microtubule bundling without completely abolishing protein expression. Such models are valuable for dissecting domain-specific functions.
Knock-in
Knock-in of fluorescent tags (e.g., GFP, mCherry) at endogenous loci allows visualization of plus-end proteins under native regulation. Tagged knock-in of EB1 or CLIP-170 enables live-cell imaging of cortical microtubule plus-ends. Knock-in of disease mutations can also model human disorders.
Overexpression
Overexpression of plus-end proteins such as Tao-1 or ARK2 can test gain-of-function effects on microtubule dynamics and cell morphology. Overexpression models are useful for identifying dominant-negative or hyperactive phenotypes.
How EDITGENE Supports cortical microtubule plus-end Research
Researchers studying cortical microtubule plus-end-related genes often need to determine whether a candidate gene is causally involved in microtubule dynamics, cortical attachment or disease. EDITGENE provides a comprehensive suite of CRISPR services to generate precisely engineered cell models, enabling functional validation of plus-end proteins in relevant biological contexts.
Contact EDITGENE today to design your custom CRISPR model for cortical microtubule plus-end research.
Frequently Asked Questions About cortical microtubule plus-end
What is GO:1903754?
GO:1903754 is the Gene Ontology term for cortical microtubule plus-end, defined as the plus-end of a cortical microtubule.
What genes are involved in cortical microtubule plus-end?
Key genes include ARK2, Gcap14, SLAIN1/2, ch-TOG, Tao-1, CLIP-170 and EB1.
What is the function of cortical microtubule plus-end?
It is the dynamic growing end of cortical microtubules that regulates microtubule polymerization, cortical attachment and exocytosis.
How do plus-end tracking proteins work?
Plus-end tracking proteins bind to the growing microtubule end and regulate its dynamics, often linking it to the actin cortex or vesicles.
What diseases are associated with cortical microtubule plus-end dysfunction?
Dysfunction is linked to neurodevelopmental disorders, axon outgrowth defects and mitotic errors in cancer.
How can I study cortical microtubule plus-end in the lab?
Live-cell imaging of fluorescent +TIPs, in vitro polymerization assays and CRISPR knockout models are common approaches.
What is the role of ARK2 at the plus-end?
ARK2 stabilizes the plus-end and promotes microtubule bundling in Arabidopsis.
How does Tao-1 regulate microtubule plus-end?
Tao-1 is a negative regulator that limits plus-end growth, likely through kinase activity.
Can CRISPR be used to study plus-end genes?
Yes, CRISPR knockout, point mutation, knock-in and overexpression are powerful tools to dissect plus-end gene function.
What model organisms are used to study cortical microtubule plus-end?
Arabidopsis, Dictyostelium, neurons and cancer cell lines are commonly used.
Conclusion
The cortical microtubule plus-end (GO:1903754) is a dynamic cellular component that serves as a hub for microtubule regulation, cortical attachment and exocytosis. Its importance spans plant development, neuronal morphogenesis and mitotic fidelity, with implications for neurodevelopmental disorders and cancer. Continued research using advanced imaging and CRISPR-based models will further elucidate the molecular mechanisms and therapeutic potential of plus-end proteins.
References
- 1. Mun DJ et al.. 2023. Gcap14 is a microtubule plus-end-tracking protein coordinating microtubule-actin crosstalk during neurodevelopment.. Proc Natl Acad Sci U S A 120(8):e2214507120 PMID: 36795749
- 2. Lan M et al.. 2023. ARK2 stabilizes the plus-end of microtubules and promotes microtubule bundling in Arabidopsis.. J Integr Plant Biol 65(1):100-116 PMID: 36169006
- 3. Scholey JM et al.. 2016. Anaphase B.. Biology (Basel) 5(4) PMID: 27941648
- 4. Noordstra I et al.. 2017. Linking cortical microtubule attachment and exocytosis.. F1000Res 6:469 PMID: 28491287
- 5. Hestermann A et al.. 2002. Centrosomal microtubule plus end tracking proteins and their role in Dictyostelium cell dynamics.. J Muscle Res Cell Motil 23(7-8):621-30 PMID: 12952061
- 6. van der Vaart B et al.. 2012. Microtubule plus-end tracking proteins SLAIN1/2 and ch-TOG promote axonal development.. J Neurosci 32(42):14722-8 PMID: 23077057
- 7. Pérez-Ferrer I et al.. 2024. Analysis of Microtubule Polymerization During Axon Outgrowth Using Fluorescently Labeled Microtubule Plus-End Tracking Proteins.. Methods Mol Biol 2831:235-249 PMID: 39134854
- 8. Liu T et al.. 2010. Tao-1 is a negative regulator of microtubule plus-end growth.. J Cell Sci 123(Pt 16):2708-16 PMID: 20647372
