GO:0008574 plus-end-directed microtubule motor activity: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0008574 describes a molecular motor activity that moves cargo toward the plus end of microtubules using energy from ATP hydrolysis.
• Kinesin superfamily proteins are the principal plus-end-directed motors, while dynein and some kinesin-like proteins such as ncd move toward the minus end.
• Plus-end-directed motility is essential for chromosome alignment, nuclear targeting of viruses, and intracellular transport.
• Kinesin-8 family members such as Kif18A use plus-end-directed activity to dampen microtubule dynamics and stabilize kinetochore-microtubule attachments.
• Bacterial pathogens can regulate host kinesin activity to promote infection, highlighting the term's role in host-pathogen interactions.
• CRISPR-based knockout, point mutation, knock-in, and overexpression models enable precise dissection of plus-end-directed motor function in disease and development.
Description
Plus-end-directed microtubule motor activity (GO:0008574) is a fundamental molecular function that drives the movement of cellular cargo toward the rapidly growing plus end of microtubules. This activity is powered by ATP hydrolysis and is primarily executed by kinesin superfamily proteins, which convert chemical energy into mechanical work to support processes such as vesicle transport, chromosome segregation, and nuclear positioning. The term is defined in QuickGO as a motor activity that generates movement along a microtubule toward the plus end, driven by ATP hydrolysis. Researchers study this activity to understand how cells organize their interior, respond to pathogens, and maintain genomic stability. Because plus-end-directed motors are involved in mitosis, intracellular trafficking, and viral infection, they represent attractive targets for therapeutic intervention and for fundamental cell biology.
plus-end-directed microtubule motor activity At A Glance
| GO ID | GO:0008574 |
|---|---|
| GO term | plus-end-directed microtubule motor activity |
| Ontology | molecular_function |
| Synonym | kinesin activity; ATP-dependent plus-end-directed microtubule motor activity; plus-end-directed kinesin ATPase activity |
| Major function | Generates movement along a microtubule toward the plus end using ATP hydrolysis |
| Directionality | Plus-end-directed (opposite to dynein and ncd minus-end motors) |
| Representative proteins | Kinesin superfamily members including Kif18A, CENP-E, and kinesin-9 family proteins |
| Cellular roles | Chromosome alignment, nuclear targeting of adenovirus, microtubule dynamics regulation, intracellular transport |
What Is GO:0008574?
In simple terms, plus-end-directed microtubule motor activity is the ability of certain proteins to walk along microtubules toward their plus ends while burning ATP for energy. According to the Gene Ontology, this molecular function enables movement along a microtubule toward the plus end, driven by ATP hydrolysis. It is synonymous with kinesin activity and ATP-dependent plus-end-directed microtubule motor activity. This activity is distinct from minus-end-directed motors, such as dynein and the Drosophila ncd protein, which move in the opposite direction.
Why Is plus-end-directed microtubule motor activity Important in Cell Biology?
Plus-end-directed microtubule motor activity is central to spatially organizing the cell and ensuring faithful cell division. It drives the transport of chromosomes, vesicles, and viruses, and its dysregulation is linked to cancer, neurodevelopmental disorders, and infectious disease. Understanding this activity at the molecular level informs drug discovery and the design of experimental models that probe motor function in health and disease.
• Enables chromosome congression and alignment during mitosis through motors such as CENP-E.
• Supports nuclear targeting of adenovirus by competing with minus-end-directed motility.
• Regulates microtubule plus-end dynamics via kinesin-8 family members like Kif18A.
• Stabilizes kinetochore-microtubule interactions in Drosophila through kinesin-8.
• Is exploited by bacterial pathogens such as Salmonella to modulate host kinesin.
• Provides a model for bidirectional transport along microtubules.
• Serves as a target for cancer therapeutics aimed at mitotic motors.
• Facilitates in vitro characterization of motor properties, as shown for Tetrahymena kinesin-9.
• Contributes to the understanding of motor directionality, contrasting with minus-end motors like ncd.
• Underpins CRISPR-based functional studies of motor proteins in disease models.
What Happens During plus-end-directed microtubule motor activity?
Motor-cargo recognition and binding
In simple terms: The motor protein first attaches to the cargo it will carry and to the microtubule track.
Plus-end-directed motors such as kinesins bind to cargo through adaptor proteins and interact with the microtubule lattice. This initial binding is regulated to ensure cargo is delivered to the correct destination. In the context of viral infection, adenovirus particles engage microtubule-dependent plus- and minus-end-directed motilities that compete for nuclear targeting.
ATP hydrolysis and conformational cycling
In simple terms: The motor burns ATP to change shape, allowing it to step along the microtubule.
ATP binding and hydrolysis drive conformational changes in the motor domain that propel the protein toward the microtubule plus end. This mechanochemical cycle is a hallmark of kinesin activity and is distinct from minus-end-directed motors such as ncd. In vitro studies of Tetrahymena kinesin-9 family members have revealed slow plus-end-directed motility, highlighting diversity in motor kinetics.
Regulation of microtubule dynamics
In simple terms: Some plus-end motors also control how microtubules grow and shrink.
Kinesin-8 family member Kif18A dampens microtubule plus-end dynamics, thereby influencing spindle architecture and chromosome movement. Drosophila kinesin-8 stabilizes kinetochore-microtubule interactions, ensuring proper chromosome segregation.
Chromosome alignment and segregation
In simple terms: Plus-end motors help line up chromosomes before cell division.
CENP-E, a plus-end-directed kinesin, facilitates chromosome alignment by transporting chromosomes along spindle microtubules. This activity is essential for mitotic fidelity and prevents aneuploidy.
Host-pathogen interactions
In simple terms: Some bacteria hijack plus-end motors to promote infection.
Salmonella can regulate host kinesin activity to manipulate intracellular trafficking, demonstrating that plus-end-directed motor activity is a target of bacterial virulence factors.
Key Genes Involved in GO:0008574 plus-end-directed microtubule motor activity
The following genes and proteins represent major plus-end-directed microtubule motors and their regulators, as supported by the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| KIF18A | Kinesin-8 motor that dampens microtubule plus-end dynamics | Mitotic spindle regulation and chromosome alignment |
| CENP-E | Kinesin motor facilitating chromosome alignment | Mitosis and aneuploidy research |
| KIF9 | Kinesin-9 family member with slow plus-end-directed motility | In vitro motor characterization |
| KIF12 | Kinesin-9 family member with slow plus-end-directed motility | In vitro motor characterization |
| ncd | Minus-end-directed kinesin-like protein in Drosophila | Contrast for plus-end motor studies |
| Dynein | Minus-end-directed microtubule motor | Bidirectional transport studies |
| Kinesin-1 | Conventional plus-end-directed motor | Intracellular transport |
| Kinesin-8 (Drosophila) | Stabilizes kinetochore-microtubule interactions | Chromosome segregation |
| Salmonella effector proteins | Regulate host kinesin activity | Host-pathogen interactions |
| Adenovirus capsid proteins | Engage plus- and minus-end motilities | Nuclear targeting |
| Tubulin | Microtubule subunit | Track for motor movement |
| ATP | Energy source for motor activity | Mechanochemical cycle |
| Kinesin light chains | Cargo adaptors for kinesin-1 | Cargo specificity |
| Kinesin heavy chains | Motor domains for plus-end movement | Force generation |
| Kif18A (mouse) | Regulates microtubule dynamics | Model for kinesin-8 function |
| CENP-E (human) | Chromosome alignment | Cancer drug targets |
| Kinesin-9 (Tetrahymena) | Slow plus-end motility | Evolutionary motor studies |
How Is plus-end-directed microtubule motor activity Regulated?
Plus-end-directed microtubule motor activity is regulated at multiple levels, including motor protein phosphorylation, cargo binding, and interactions with microtubule-associated proteins. For example, Salmonella can modulate host kinesin activity to promote infection. Kinesin-8 family members such as Kif18A are regulated to control microtubule dynamics during mitosis. Bidirectional transport along microtubules involves coordination between plus-end and minus-end motors, ensuring proper cargo distribution.
plus-end-directed microtubule motor activity and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CENP-E | Cancer, chromosome instability | Knockout and point mutation in cancer cell lines |
| KIF18A | Cancer, mitotic defects | Knockout and overexpression in HeLa cells |
| Kinesin-8 (Drosophila) | Chromosome segregation errors | Knock-in and knockout in Drosophila |
| Kinesin-9 (Tetrahymena) | Motility defects | Overexpression and point mutation |
| ncd | Motor directionality defects | Knockout in Drosophila |
Cancer and mitotic dysregulation
Plus-end-directed motors such as CENP-E and Kif18A are critical for chromosome alignment and spindle assembly. Their dysfunction can lead to aneuploidy and cancer, making them potential therapeutic targets.
Neurodegeneration and transport defects
Defects in microtubule-based transport, including plus-end-directed motility, are implicated in neurodegenerative diseases where axonal transport is impaired.
Infectious disease and host-pathogen interactions
Pathogens like Salmonella and adenovirus exploit plus-end-directed motor activity for intracellular movement and nuclear targeting, highlighting roles in infectious disease.
From plus-end-directed microtubule motor activity-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of KIF18A affect microtubule dynamics? | KIF18A knockout cell line |
| How does CENP-E point mutation affect chromosome alignment? | CENP-E point mutation knock-in |
| Can kinesin-9 motility be altered by mutation? | Tetrahymena kinesin-9 point mutation |
| Does overexpression of Kif18A stabilize kinetochore-microtubule attachments? | Drosophila kinesin-8 overexpression |
| How does Salmonella regulate host kinesin? | Salmonella infection model with kinesin knockout |
| What is the role of plus-end motors in adenovirus nuclear targeting? | Adenovirus infection with motor knockdown |
How to Study the plus-end-directed microtubule motor activity Process
| Method | What It Measures | Typical Application |
|---|---|---|
| In vitro motility assay | Motor velocity and directionality | Characterizing kinesin-9 |
| Live-cell imaging | Cargo transport and chromosome dynamics | Mitosis studies |
| CRISPR knockout screen | Gene essentiality for motor function | Identifying novel regulators |
| ATPase assay | ATP hydrolysis rate | Motor kinetics |
| Immunofluorescence | Localization of motors and microtubules | Spindle assembly |
| Co-immunoprecipitation | Protein-protein interactions | Cargo adaptor identification |
| RNA-seq | Transcriptional changes upon motor perturbation | Pathway analysis |
| Proteomics | Global protein expression changes | Motor network mapping |
In vitro motility assays
Recombinant motor proteins can be tested for plus-end-directed movement using microtubule gliding or single-molecule assays, as demonstrated for Tetrahymena kinesin-9.
Live-cell imaging
Fluorescently tagged motors and microtubules allow real-time visualization of plus-end-directed transport and chromosome alignment.
CRISPR-based genetic screens
Pooled knockout screens can identify genes required for plus-end-directed motor activity and related processes.
Biochemical ATPase assays
Measuring ATP hydrolysis rates provides quantitative readouts of motor activity and regulation.
How CRISPR Can Be Used to Study GO:0008574 plus-end-directed microtubule motor activity
Knockout
CRISPR knockout of plus-end-directed motor genes such as KIF18A or CENP-E enables loss-of-function studies to assess their role in mitosis and transport.
Point Mutation
Introducing specific point mutations in motor domains can dissect ATP hydrolysis and microtubule binding without abolishing protein expression.
Knock-in
Knock-in of tagged motors (e.g., GFP) allows real-time imaging of plus-end-directed movement in live cells.
Overexpression
Overexpression of plus-end motors can reveal dominant effects on microtubule dynamics and cargo distribution.
How EDITGENE Supports plus-end-directed microtubule motor activity Research
Researchers studying plus-end-directed microtubule motor activity-related genes often need to determine whether a candidate gene is causally involved in transport, mitosis, or disease. EDITGENE provides a comprehensive suite of CRISPR services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for plus-end-directed microtubule motor activity research.
Frequently Asked Questions About plus-end-directed microtubule motor activity
What is plus-end-directed microtubule motor activity?
It is a molecular function (GO:0008574) that moves cargo toward the plus end of microtubules using ATP hydrolysis, primarily performed by kinesin proteins.
What genes are involved in plus-end-directed microtubule motor activity?
Key genes include KIF18A, CENP-E, kinesin-9 family members, and conventional kinesin-1.
How does plus-end-directed motor activity differ from minus-end-directed activity?
Plus-end motors move toward the growing end of microtubules, while minus-end motors such as dynein and ncd move in the opposite direction.
What diseases are associated with plus-end-directed microtubule motor activity?
Dysregulation is linked to cancer, neurodegeneration, and infectious diseases.
How can I study plus-end-directed microtubule motor activity in the lab?
In vitro motility assays, live-cell imaging, and CRISPR screens are common approaches.
What is the role of KIF18A in plus-end-directed motility?
KIF18A is a kinesin-8 that dampens microtubule plus-end dynamics and regulates chromosome alignment.
How does CENP-E contribute to chromosome alignment?
CENP-E is a plus-end-directed motor that transports chromosomes along spindle microtubules during mitosis.
Can bacteria regulate plus-end-directed motor activity?
Yes, Salmonella can modulate host kinesin activity to promote infection.
What experimental models are used to study plus-end-directed motors?
Knockout, point mutation, knock-in, and overexpression models in cell lines and Drosophila are widely used.
What CRISPR services does EDITGENE offer for motor research?
EDITGENE provides knockout, point mutation, knock-in, overexpression, library screening, and bioinformatics services.
Conclusion
Plus-end-directed microtubule motor activity (GO:0008574) is a cornerstone of intracellular organization, driving chromosome alignment, cargo transport, and host-pathogen interactions. Its molecular mechanisms and regulatory networks are best dissected using CRISPR-based models and advanced imaging. EDITGENE offers the tools to accelerate discoveries in this dynamic field.
References
- 1. Welte MA. 2004. Bidirectional transport along microtubules.. Curr Biol 14(13):R525-37 PMID: 15242636
- 2. Ishii H et al.. 2024. Two Tetrahymena kinesin-9 family members exhibit slow plus-end-directed motility in vitro.. Sci Rep 14(1):20993 PMID: 39251704
- 3. Leone P et al.. 2011. Kinesin regulation by Salmonella.. Virulence 2(1):63-6 PMID: 21217202
- 4. Craske B et al.. 2020. Leaving no-one behind: how CENP-E facilitates chromosome alignment.. Essays Biochem 64(2):313-324 PMID: 32347304
- 5. Du Y et al.. 2010. The kinesin-8 Kif18A dampens microtubule plus-end dynamics.. Curr Biol 20(4):374-80 PMID: 20153196
- 6. Suomalainen M et al.. 1999. Microtubule-dependent plus- and minus end-directed motilities are competing processes for nuclear targeting of adenovirus.. J Cell Biol 144(4):657-72 PMID: 10037788
- 7. Edzuka T et al.. 2019. Drosophila kinesin-8 stabilizes the kinetochore-microtubule interaction.. J Cell Biol 218(2):474-488 PMID: 30538142
- 8. McDonald HB et al.. 1990. The kinesin-like ncd protein of Drosophila is a minus end-directed microtubule motor.. Cell 63(6):1159-65 PMID: 2261638
