GO:0035735 intraciliary transport involved in cilium assembly: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0035735 describes the bidirectional movement of large protein complexes along microtubules within a cilium that contributes to cilium assembly.
• Intraciliary transport, also called intraflagellar transport (IFT), is essential for building and maintaining cilia and flagella.
• The process relies on kinesin-2 and cytoplasmic dynein motors moving IFT trains between the ciliary base and tip.
• Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus nonciliated cells.
• Disruption of IFT causes ciliopathies, including retinal degeneration, skeletal abnormalities, and kidney disease.
• CRISPR knockout, knock-in, and overexpression models are key tools for dissecting IFT gene function.
Description
Intraciliary transport involved in cilium assembly (GO:0035735) is the biological process that moves large protein complexes bidirectionally along microtubules inside a cilium to build and maintain the organelle. This process, widely known as intraflagellar transport (IFT), is conserved from algae to humans and is required for the assembly of nearly all cilia and flagella. Because cilia are essential for sensing and signaling, defects in IFT underlie a broad class of human diseases called ciliopathies. Researchers studying cilia, developmental signaling, and ciliopathies need a precise understanding of GO:0035735 to interpret gene function and design experiments. Recent work shows that transcriptional programs, such as those controlled by the NSL complex, diversify IFT functions between ciliated and nonciliated cells, adding another layer of regulation.
intraciliary transport involved in cilium assembly At A Glance
| GO ID | GO:0035735 |
|---|---|
| GO term | intraciliary transport involved in cilium assembly |
| Ontology | biological_process |
| Synonym | intraflagellar transport; intraciliary transport involved in cilium morphogenesis; intraflagellar transport involved in cilium morphogenesis |
| Major function | Bidirectional movement of large protein complexes along microtubules within a cilium that contributes to cilium assembly |
| Related cellular component | Cilium; ciliary tip; ciliary base; IFT particles |
| Related molecular functions | Microtubule motor activity; protein binding |
| Key motors | Kinesin-2 (anterograde); cytoplasmic dynein-2 (retrograde) |
| Associated diseases | Ciliopathies such as retinal degeneration, skeletal dysplasias, and kidney disease |
What Is GO:0035735?
According to the Gene Ontology, GO:0035735 is defined as the bidirectional movement of large protein complexes along microtubules within a cilium that contributes to cilium assembly. In simpler terms, it is the internal train system that carries building blocks and signaling molecules up and down the cilium to keep it growing and working.
Why Is intraciliary transport involved in cilium assembly Important in Cell Biology?
GO:0035735 is essential because cilia cannot be assembled or maintained without IFT, and cilia are critical for vision, smell, hearing, kidney function, and developmental signaling. Mutations in IFT genes cause a wide spectrum of ciliopathies, and understanding this process provides mechanistic insight into these disorders. Moreover, recent evidence indicates that IFT functions are transcriptionally diversified between ciliated and nonciliated cells, which has implications for tissue-specific disease phenotypes.
• Required for the assembly and maintenance of all cilia and flagella.
• Mutations in IFT components cause ciliopathies, including retinal degeneration and skeletal abnormalities.
• IFT is critical for Hedgehog signaling during development.
• Dysregulation of IFT is linked to kidney disease and obesity.
• Transcriptional regulation by the NSL complex diversifies IFT functions in different cell types.
• IFT is a target for understanding cancer, as cilia are lost in many tumors.
• Modeling IFT gene mutations helps identify genotype-phenotype correlations.
• CRISPR screens can uncover novel IFT regulators and cargo adaptors.
What Happens During intraciliary transport involved in cilium assembly?
Anterograde transport (base to tip)
In simple terms: The train carries cargo from the cell body to the tip of the cilium.
Anterograde intraflagellar transport moves IFT particles and their cargo from the ciliary base to the tip using kinesin-2 motors. This step delivers axonemal precursors, membrane proteins, and signaling molecules required for cilium assembly and maintenance.
Retrograde transport (tip to base)
In simple terms: The train returns from the tip back to the cell body, recycling components.
Retrograde intraflagellar transport is powered by cytoplasmic dynein-2 and carries IFT trains, turnover products, and signaling molecules back to the ciliary base. This recycling is essential for maintaining a steady-state cilium and for removing damaged components.
Cargo sorting and delivery
In simple terms: The train must load the right cargo at the right time.
IFT particles recognize and bind specific cargoes, including tubulin, axonemal dynein, and signaling receptors, through adaptor proteins. Proper cargo sorting ensures that building blocks reach the ciliary tip for assembly.
Cilium assembly and maintenance
In simple terms: The constant movement of trains builds and repairs the cilium.
The coordinated action of anterograde and retrograde transport provides the materials and turnover necessary for cilium assembly and maintenance. Disruption of either direction leads to shortened or dysfunctional cilia.
Key Genes Involved in GO:0035735 intraciliary transport involved in cilium assembly
The following genes encode core components of the intraciliary transport machinery and its regulation.
| Gene | Major Role | Research Relevance |
|---|---|---|
| IFT88 | Core IFT particle protein; anterograde transport | Knockout causes cilia assembly defects; models for ciliopathies |
| IFT20 | IFT particle component; cargo recognition | Involved in ciliary trafficking and signaling |
| IFT27 | Small GTPase; IFT particle assembly | Mutations linked to skeletal ciliopathies |
| IFT46 | IFT particle protein; interacts with kinesin-2 | Required for efficient anterograde transport |
| IFT57 | IFT particle protein; retrograde transport | Knockout leads to cilia loss and developmental defects |
| IFT80 | IFT particle protein; involved in Hedgehog signaling | Mutations cause Jeune syndrome |
| IFT81 | IFT particle protein; cargo adaptor | Associated with skeletal ciliopathies |
| IFT122 | IFT particle protein; retrograde transport | Mutations cause cranioectodermal dysplasia |
| IFT140 | IFT particle protein; retrograde transport | Defects lead to retinal degeneration |
| KIF3A | Kinesin-2 motor subunit; anterograde transport | Essential for cilia formation; knockout is embryonic lethal |
| KIF3B | Kinesin-2 motor subunit; anterograde transport | Required for left-right asymmetry |
| DYNC2H1 | Cytoplasmic dynein-2 heavy chain; retrograde transport | Mutations cause short-rib polydactyly syndrome |
| DYNC2LI1 | Dynein-2 light intermediate chain; retrograde transport | Associated with skeletal ciliopathies |
| TTC21B | IFT-A component; retrograde transport | Mutations linked to nephronophthisis |
| WDR19 | IFT-A component; retrograde transport | Causes cranioectodermal dysplasia and retinal dystrophy |
| NSL complex | Transcriptional regulation of IFT genes | Diversifies IFT functions in ciliated vs nonciliated cells |
How Is intraciliary transport involved in cilium assembly Regulated?
Transcription of IFT genes is regulated by the NSL complex, which enables diversification of IFT functions in ciliated versus nonciliated cells. This transcriptional control ensures that ciliated cells express the appropriate repertoire of IFT components for cilium assembly and maintenance.
intraciliary transport involved in cilium assembly and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| IFT88 | Ciliopathy; retinal degeneration | Knockout mouse; patient-derived iPSCs |
| DYNC2H1 | Short-rib polydactyly syndrome | Point-mutation knock-in mouse |
| IFT140 | Retinal degeneration; skeletal ciliopathy | Conditional knockout mouse |
| TTC21B | Nephronophthisis | Knockout zebrafish; organoids |
| WDR19 | Cranioectodermal dysplasia | CRISPR knock-in of patient mutations |
Ciliopathies
Mutations in genes encoding intraciliary transport components cause a broad range of ciliopathies, including retinal degeneration, skeletal dysplasias, and kidney disease. These disorders highlight the essential role of GO:0035735 in human health.
Retinal degeneration
Defects in IFT lead to photoreceptor cell death and retinal degeneration, as the connecting cilium of photoreceptors relies on IFT for protein trafficking.
Skeletal dysplasias
Impaired IFT disrupts Hedgehog signaling, causing skeletal abnormalities such as short ribs and polydactyly.
Cancer
Loss of cilia is observed in many cancers, and dysregulation of IFT genes can contribute to tumorigenesis by altering signaling pathways.
From intraciliary transport involved in cilium assembly-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of IFT88 abolish cilia assembly? | CRISPR knockout in cultured cells |
| Does a patient mutation in DYNC2H1 impair retrograde transport? | Point-mutation knock-in in mouse |
| Can wild-type IFT140 rescue cilia defects? | Knock-in of tagged IFT140 |
| Does overexpression of KIF3A increase cilia length? | Overexpression cell line |
| Which IFT genes are regulated by NSL complex? | Transcriptional profiling with knockout |
| Can CRISPR screen identify novel IFT regulators? | Genome-wide CRISPR library screening |
How to Study the intraciliary transport involved in cilium assembly Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell imaging | Movement of IFT particles | Anterograde/retrograde transport dynamics |
| RNA-seq | Transcriptional changes | Identifying IFT gene regulation |
| Proteomics | Protein interactions | Mapping IFT particle composition |
| Immunofluorescence | Cilia presence and length | Assessing ciliogenesis defects |
| CRISPR knockout | Gene function loss | Determining requirement for IFT genes |
| CRISPR knock-in | Tagged or mutant protein expression | Studying patient mutations |
| Overexpression | Gain-of-function effects | Testing sufficiency of IFT components |
| CRISPR library screening | Genome-wide fitness | Discovering novel IFT regulators |
Imaging of IFT trains
Live-cell fluorescence microscopy and kymography allow visualization of IFT particle movement along cilia, providing direct evidence of anterograde and retrograde transport.
Transcriptomics and RNA-seq
RNA sequencing can reveal transcriptional changes in IFT genes upon perturbation, such as NSL complex knockout, uncovering regulatory networks.
Proteomics and interactomics
Affinity purification coupled with mass spectrometry identifies IFT particle components and cargo adaptors, helping to define the molecular architecture of the transport machinery.
Functional assays for ciliogenesis
Serum starvation and immunofluorescence for acetylated alpha-tubulin are standard methods to assess cilia formation and length after genetic manipulation.
How CRISPR Can Be Used to Study GO:0035735 intraciliary transport involved in cilium assembly
Knockout
CRISPR knockout of IFT genes such as IFT88 or KIF3A abolishes cilia assembly, providing definitive evidence for their essential roles in GO:0035735.
Point Mutation
Introducing patient-specific point mutations (e.g., in DYNC2H1) via CRISPR allows modeling of ciliopathies and assessment of transport defects.
Knock-in
Knock-in of tagged IFT proteins (e.g., GFP-IFT20) enables live-cell imaging and biochemical isolation of transport complexes.
Overexpression
Overexpression of IFT components can test whether increased levels enhance cilia assembly or rescue loss-of-function phenotypes.
How EDITGENE Supports intraciliary transport involved in cilium assembly Research
Researchers studying intraciliary transport involved in cilium assembly-related genes often need to determine whether a candidate gene is causally involved in cilia formation, cargo trafficking, or disease phenotypes. EDITGENE provides comprehensive CRISPR-based services to accelerate this discovery process.
Contact EDITGENE today to design your custom CRISPR model for intraciliary transport involved in cilium assembly research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PCM1 Knockout HEK293 Cell Line | EDJ-KQ2932 | Human | 5108 | Details Get a Quote |
| SSX2IP Knockout HEK293 Cell Line | EDJ-KQ7600 | Human | 117178 | Details Get a Quote |
| IFT81 Knockout HEK293 Cell Line | EDJ-KQ8950 | Human | 28981 | Details Get a Quote |
| IFT74 Knockout HEK293 Cell Line | EDJ-KQ9476 | Human | 80173 | Details Get a Quote |
| DYNC2LI1 Knockout HEK293 Cell Line | EDJ-KQ11162 | Human | 51626 | Details Get a Quote |
| IFT56 Knockout HEK293 Cell Line | EDJ-KQ13068 | Human | 79989 | Details Get a Quote |
| PCM1 Knockout HCT 116 Cell Line | EDJ-KQ24045 | Human | 5108 | Details Get a Quote |
| PCM1 Knockout HeLa Cell Line | EDJ-KQ24046 | Human | 5108 | Details Get a Quote |
| SSX2IP Knockout A-549 Cell Line | EDJ-KQ32940 | Human | 117178 | Details Get a Quote |
| SSX2IP Knockout HCT 116 Cell Line | EDJ-KQ32941 | Human | 117178 | Details Get a Quote |
| SSX2IP Knockout HeLa Cell Line | EDJ-KQ32942 | Human | 117178 | Details Get a Quote |
| IFT74 Knockout A-549 Cell Line | EDJ-KQ36185 | Human | 80173 | Details Get a Quote |
| IFT74 Knockout HCT 116 Cell Line | EDJ-KQ36186 | Human | 80173 | Details Get a Quote |
| IFT74 Knockout HeLa Cell Line | EDJ-KQ36187 | Human | 80173 | Details Get a Quote |
| DYNC2LI1 Knockout A-549 Cell Line | EDJ-KQ39174 | Human | 51626 | Details Get a Quote |
Displaying Records 1 To 15 Of 28 Records
Frequently Asked Questions About intraciliary transport involved in cilium assembly
What is intraciliary transport involved in cilium assembly?
It is the bidirectional movement of large protein complexes along microtubules within a cilium that contributes to cilium assembly, also known as intraflagellar transport.
What genes are involved in intraciliary transport?
Key genes include IFT88, IFT20, IFT27, IFT46, IFT57, IFT80, IFT81, IFT122, IFT140, KIF3A, KIF3B, DYNC2H1, DYNC2LI1, TTC21B, and WDR19.
What is the function of GO:0035735?
GO:0035735 describes the process that moves building blocks and signaling molecules along the cilium to assemble and maintain the organelle.
How is intraciliary transport regulated?
It is regulated transcriptionally by complexes such as the NSL complex, which diversifies IFT functions in ciliated versus nonciliated cells.
What diseases are associated with defects in intraciliary transport?
Defects cause ciliopathies, including retinal degeneration, skeletal dysplasias, kidney disease, and some cancers.
What motors drive intraciliary transport?
Kinesin-2 drives anterograde transport from base to tip, while cytoplasmic dynein-2 drives retrograde transport from tip to base.
How can I study intraciliary transport in the lab?
Common methods include live-cell imaging, RNA-seq, proteomics, immunofluorescence for cilia, and CRISPR knockout or knock-in models.
What is the role of IFT88 in cilia?
IFT88 is a core IFT particle protein required for anterograde transport and cilia assembly; its knockout abolishes cilia.
Can CRISPR be used to model ciliopathies?
Yes, CRISPR knockout, point mutation, and knock-in models are widely used to study IFT gene mutations and ciliopathy phenotypes.
What is the difference between anterograde and retrograde IFT?
Anterograde transport moves particles from the ciliary base to the tip using kinesin-2, while retrograde transport returns them using dynein-2.
Conclusion
GO:0035735, intraciliary transport involved in cilium assembly, is a fundamental biological process required for cilia formation and function. Its molecular machinery, including IFT particles and motor proteins, is conserved and essential for human health. Disruption of this process leads to a spectrum of ciliopathies, making it a critical area of research. Advanced CRISPR models and multi-omics approaches continue to unravel the complexities of IFT regulation and its role in disease.
References
- 1. Tsang TH et al.. 2023. Transcriptional regulation by the NSL complex enables diversification of IFT functions in ciliated versus nonciliated cells.. Sci Adv 9(34):eadh5598 PMID: 37624894
