GO:0045103 intermediate filament-based process: Cytoskeletal Organization, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0045103 (intermediate filament-based process) describes any cellular process that depends upon or alters the intermediate filament cytoskeleton, including filament assembly, disassembly, and interactions with associated proteins.
• Intermediate filaments are encoded by a large multigene family (e.g., KRT6C, KRT9, and others) whose expression is highly tissue-specific and frequently altered in cancer and genetic skin disorders [2, 5].
• Dysregulation of intermediate filament-based processes contributes to tumor progression, including breast ductal carcinoma in situ progression to invasive ductal carcinoma and colorectal cancer.
• Bioinformatics and high-throughput sequencing approaches have identified intermediate filament genes as key players in metabolic and reproductive disorders, such as type 2 diabetes-induced erectile dysfunction.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal interrogation of intermediate filament genes in relevant cellular contexts.
• Understanding GO:0045103 requires integrating proteomics, imaging, and functional genomics to resolve how intermediate filaments contribute to cell mechanics, signaling, and disease.
Description
The intermediate filament cytoskeleton is a major component of the eukaryotic cytoskeleton, providing mechanical support and regulating diverse cellular processes. GO:0045103, intermediate filament-based process, is defined as any cellular process that depends upon or alters the intermediate filament cytoskeleton, that part of the cytoskeleton comprising intermediate filaments and their associated proteins. This term captures the dynamic and context-dependent roles of intermediate filaments in cell shape, motility, and tissue integrity. Research has shown that intermediate filament proteins such as KRT6C and KRT9 are involved in genetic cutaneous disorders, highlighting the clinical relevance of these processes. Furthermore, proteomic profiling has revealed that KRT6C may act as a heterodimer partner for KRT9, providing new insights into the classification of epidermolytic palmoplantar keratoderma and pachyonychia congenita. These findings underscore the importance of intermediate filament-based processes in both normal physiology and disease. In cancer, aberrant expression of intermediate filament genes has been linked to breast ductal carcinoma in situ progression to invasive ductal carcinoma and colorectal cancer. Additionally, high-throughput sequencing has identified key genes related to intermediate filament processes in type 2 diabetes-induced erectile dysfunction. Thus, GO:0045103 represents a critical area of research for understanding cytoskeletal contributions to human health and disease.
intermediate filament-based process At A Glance
| GO ID | GO:0045103 |
|---|---|
| GO term | intermediate filament-based process |
| Ontology | biological_process |
| Synonym | None |
| Major function | Cellular processes dependent on or altering the intermediate filament cytoskeleton |
| Definition | Any cellular process that depends upon or alters the intermediate filament cytoskeleton, that part of the cytoskeleton comprising intermediate filaments and their associated proteins. |
| Related cellular component | Intermediate filament cytoskeleton |
| Related molecular function | Structural constituent of cytoskeleton (e.g., intermediate filament proteins) |
| Research relevance | Implicated in cancer progression, genetic skin disorders, and metabolic diseases [2, 4, 5, 7] |
What Is GO:0045103?
GO:0045103, intermediate filament-based process, refers to any cellular process that depends upon or alters the intermediate filament cytoskeleton. This includes the assembly, disassembly, and reorganization of intermediate filaments, as well as their interactions with associated proteins that modulate their function. The term encompasses processes such as filament dynamics, crosslinking, and signaling events that are mediated by or affect intermediate filaments. It is a biological process ontology term that highlights the functional roles of intermediate filaments beyond mere structural support.
Why Is intermediate filament-based process Important in Cell Biology?
Intermediate filament-based processes are fundamental to cell and tissue mechanics, and their dysregulation is associated with a wide range of human diseases, including cancer, skin disorders, and metabolic conditions. Understanding GO:0045103 provides insights into how cells maintain structural integrity and respond to stress, and it offers potential targets for therapeutic intervention. The tissue-specific expression of intermediate filament genes makes them valuable biomarkers and research tools, as demonstrated by studies linking KRT6C and KRT9 to genetic cutaneous disorders and by bioinformatic analyses identifying intermediate filament genes in cancer progression [4, 5].
• Intermediate filaments provide mechanical stability to cells and tissues, and their dysfunction leads to fragility and disease.
• Mutations in intermediate filament genes cause genetic skin disorders such as epidermolytic palmoplantar keratoderma and pachyonychia congenita.
• Altered intermediate filament expression is observed in breast ductal carcinoma in situ progression to invasive ductal carcinoma.
• Bioinformatics analyses have implicated intermediate filament genes in colorectal cancer.
• High-throughput sequencing has identified intermediate filament-related genes in type 2 diabetes-induced erectile dysfunction.
• Intermediate filament-based processes are involved in cell migration and metastasis, as suggested by studies on metastasizing cells.
• They serve as important markers for tissue differentiation and cancer subtyping.
• CRISPR-based editing enables functional dissection of intermediate filament genes in disease models.
• Proteomic profiling can reveal intermediate filament interaction networks and heterodimer partners.
• Understanding these processes can guide development of targeted therapies for skin and cancer disorders [2, 4].
What Happens During intermediate filament-based process?
Intermediate Filament Assembly and Dynamics
In simple terms: Intermediate filaments are built from proteins that twist together to form strong cables inside cells.
Intermediate filament assembly involves the polymerization of intermediate filament proteins (e.g., keratins, vimentin) into 10-nm filaments. This process is regulated by phosphorylation and interactions with associated proteins. Proteomic studies have identified KRT6C as a probable heterodimer partner for KRT9, suggesting that specific pairing is crucial for filament formation in skin. The dynamic remodeling of these filaments is essential for cellular responses to mechanical stress and is a key aspect of GO:0045103.
Regulation by Associated Proteins
In simple terms: Other proteins can attach to intermediate filaments and change how they behave.
Intermediate filament-based processes are modulated by associated proteins that can crosslink, bundle, or sever filaments. For example, in cancer, aberrant expression of intermediate filament genes may alter interactions with signaling proteins, contributing to progression. Bioinformatics analyses have highlighted the possible role of SRMS in colorectal cancer, potentially through effects on cytoskeletal organization.
Role in Cell Migration and Metastasis
In simple terms: Intermediate filaments help cells move and can be involved in cancer spread.
Intermediate filaments contribute to cell migration by providing structural support and anchoring organelles. A novel pipeline employing deep multi-attention channels network for autonomous detection of metastasizing cells through fluorescence microscopy has been developed, which may aid in studying intermediate filament dynamics during metastasis. This underscores the relevance of GO:0045103 in cancer biology.
Intermediate Filaments in Metabolic and Reproductive Disorders
In simple terms: Intermediate filaments are also important in conditions like diabetes-related erectile dysfunction.
High-throughput sequencing and bioinformatic analysis identified key genes in type 2 diabetes-induced erectile dysfunction rats with stem cell therapy, including those related to intermediate filament processes. This suggests that GO:0045103 extends beyond structural roles to influence metabolic and reproductive functions.
Key Genes Involved in GO:0045103 intermediate filament-based process
The following genes and proteins are central to intermediate filament-based processes, as supported by the verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| KRT6C | Intermediate filament protein; heterodimer partner for KRT9 | Implicated in epidermolytic palmoplantar keratoderma and pachyonychia congenita |
| KRT9 | Intermediate filament protein; forms heterodimers with KRT6C | Mutations cause epidermolytic palmoplantar keratoderma |
| SRMS | Non-receptor tyrosine kinase; possible role in cytoskeletal regulation | Bioinformatics analysis suggests involvement in colorectal cancer |
| VIM | Vimentin; type III intermediate filament protein | Marker of epithelial-mesenchymal transition; studied in cancer progression |
| KRT8 | Type II keratin; pairs with KRT18 | Expressed in simple epithelia; altered in breast cancer |
| KRT18 | Type I keratin; pairs with KRT8 | Commonly used as epithelial marker; implicated in cancer |
| KRT5 | Type II keratin; pairs with KRT14 | Mutations cause epidermolysis bullosa simplex |
| KRT14 | Type I keratin; pairs with KRT5 | Mutations cause epidermolysis bullosa simplex |
| LMNA | Lamin A/C; nuclear intermediate filament protein | Mutations cause laminopathies; studied in mechanotransduction |
| DES | Desmin; muscle-specific intermediate filament | Involved in desmin-related myopathies |
| GFAP | Glial fibrillary acidic protein; astrocyte intermediate filament | Marker of astrogliosis; implicated in neurodegeneration |
| NEFL | Neurofilament light polypeptide | Biomarker for neuroaxonal damage |
| NEFM | Neurofilament medium polypeptide | Component of neurofilaments |
| NEFH | Neurofilament heavy polypeptide | Component of neurofilaments |
| PRPH | Peripherin; type III intermediate filament | Expressed in peripheral neurons |
| KRT7 | Type II keratin; expressed in glandular epithelia | Marker for various carcinomas |
| KRT19 | Type I keratin; small epithelial cells | Used as a marker for circulating tumor cells |
| KRT20 | Type I keratin; intestinal epithelium | Marker for colorectal cancer |
How Is intermediate filament-based process Regulated?
Intermediate filament-based processes are regulated at multiple levels, including gene expression, post-translational modifications (e.g., phosphorylation), and interactions with associated proteins. For instance, microRNAs have been implicated in the regulation of intermediate filament genes in perirenal adipose tissue of rabbits fed a high-fat diet. Additionally, whole genome scans in African Ankole cattle have revealed genetic signatures that may include intermediate filament genes related to beef quality. These findings suggest that both transcriptional and post-transcriptional mechanisms control intermediate filament dynamics in response to physiological and environmental cues.
intermediate filament-based process and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| KRT6C | Epidermolytic palmoplantar keratoderma; pachyonychia congenita | Knockout or point mutation in keratinocytes |
| KRT9 | Epidermolytic palmoplantar keratoderma | Knock-in of patient mutations in cell lines |
| SRMS | Colorectal cancer | Knockout in colorectal cancer cell lines |
| VIM | Breast cancer progression | Overexpression or knockout in breast cancer cells |
| KRT8/KRT18 | Epithelial cancers | Knockout in epithelial cell lines |
Intermediate Filament-Based Processes in Genetic Skin Disorders
Mutations in intermediate filament genes such as KRT6C and KRT9 cause genetic cutaneous disorders, including epidermolytic palmoplantar keratoderma and a milder form of pachyonychia congenita. Proteomic profiling has revealed that KRT6C is a probable heterodimer partner for KRT9, providing new insights into re-classifying these disorders. This highlights the critical role of intermediate filament-based processes in skin integrity.
Intermediate Filament-Based Processes in Cancer
Aberrant expression of intermediate filament genes is associated with cancer progression. In breast ductal carcinoma in situ progression to invasive ductal carcinoma, identification of aberrant gene expression has implicated intermediate filament genes. Similarly, bioinformatics analysis suggests a possible role of SRMS in colorectal cancer, potentially through cytoskeletal regulation. These findings underscore the importance of GO:0045103 in oncology.
Intermediate Filament-Based Processes in Metabolic and Reproductive Disorders
High-throughput sequencing and bioinformatic analysis identified key genes in type 2 diabetes-induced erectile dysfunction rats with stem cell therapy, including those related to intermediate filament processes. This suggests that intermediate filament-based processes may contribute to metabolic and reproductive pathologies.
From intermediate filament-based process-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of KRT6C affect intermediate filament assembly? | KRT6C knockout keratinocytes |
| Does a specific KRT9 mutation cause dominant-negative effects? | Point mutation knock-in in keratinocytes |
| Can wild-type KRT6C rescue KRT9 mutant phenotypes? | Knock-in of wild-type KRT6C in mutant cells |
| Where does KRT6C localize in live cells? | Tagged knock-in of KRT6C with fluorescent protein |
| Does overexpression of SRMS alter cytoskeletal dynamics? | Overexpression of SRMS in colorectal cancer cells |
| Can CRISPR library screening identify modifiers of intermediate filament-based processes? | Genome-wide CRISPR knockout library in relevant cell lines |
How to Study the intermediate filament-based process Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Proteomics | Protein interactions and modifications | Identifying heterodimer partners like KRT6C/KRT9 |
| RNA-seq | Gene expression changes | Identifying aberrant intermediate filament gene expression in cancer |
| Bioinformatics analysis | Gene networks and pathways | Discovering key genes in colorectal cancer |
| High-throughput sequencing | Genetic variants and expression | Studying type 2 diabetes-induced erectile dysfunction |
| Fluorescence microscopy | Cellular localization and dynamics | Detecting metastasizing cells |
| Whole genome scan | Genetic signatures | Identifying selection signatures in cattle |
| MicroRNA profiling | Regulatory microRNAs | Studying adipose tissue in high-fat diet |
| CRISPR screening | Gene function on a genome-wide scale | Identifying modifiers of intermediate filament processes |
Proteomic Profiling
Proteomic profiling can identify interaction partners and post-translational modifications of intermediate filament proteins. For example, proteomic profiling revealed KRT6C as a probable heterodimer partner for KRT9, providing insights into genetic cutaneous disorders.
High-Throughput Sequencing and Bioinformatics
High-throughput sequencing combined with bioinformatic analysis can identify key genes and regulatory networks involving intermediate filament-based processes. This approach has been used to identify key genes in type 2 diabetes-induced erectile dysfunction and to analyze microRNAs in perirenal adipose tissue.
Fluorescence Microscopy and Imaging
Fluorescence microscopy enables visualization of intermediate filament dynamics and cell morphology. A novel pipeline employing deep multi-attention channels network for autonomous detection of metastasizing cells through fluorescence microscopy has been developed, which can be applied to study intermediate filament-based processes in metastasis.
Genome-Wide Association and Whole Genome Scans
Whole genome scans can reveal genetic signatures associated with intermediate filament genes. For instance, a whole genome scan in African Ankole cattle revealed genetic signatures potentially related to beef quality, which may involve intermediate filament genes.
How CRISPR Can Be Used to Study GO:0045103 intermediate filament-based process
Knockout
CRISPR knockout of intermediate filament genes (e.g., KRT6C, KRT9) can reveal their essential roles in filament assembly and cellular mechanics. For example, knocking out KRT6C in keratinocytes may disrupt heterodimer formation with KRT9, mimicking aspects of genetic skin disorders.
Point Mutation
Introducing disease-associated point mutations (e.g., in KRT9) via CRISPR can model dominant-negative effects and elucidate molecular mechanisms of epidermolytic palmoplantar keratoderma.
Knock-in
Knock-in of wild-type or tagged intermediate filament genes allows rescue experiments and live-cell imaging. For instance, tagging KRT6C with a fluorescent protein can track its localization and dynamics in real time.
Overexpression
Overexpression of intermediate filament genes (e.g., SRMS) can test gain-of-function effects on cytoskeletal organization and cancer phenotypes, as suggested by bioinformatics analysis in colorectal cancer.
How EDITGENE Supports intermediate filament-based process Research
Researchers studying intermediate filament-based process-related genes often need to determine whether a candidate gene is causally involved in cytoskeletal dynamics, disease progression, or cellular stress responses. EDITGENE provides comprehensive CRISPR services to enable such functional studies.
Contact EDITGENE today to design your custom CRISPR model for intermediate filament-based process research.
Frequently Asked Questions About intermediate filament-based process
What is GO:0045103?
GO:0045103 is the Gene Ontology term for intermediate filament-based process, defined as any cellular process that depends upon or alters the intermediate filament cytoskeleton.
What genes are involved in intermediate filament-based process?
Key genes include KRT6C, KRT9, VIM, KRT8, KRT18, and others encoding intermediate filament proteins and associated factors [2, 5].
How are intermediate filament-based processes studied?
They are studied using proteomics, high-throughput sequencing, bioinformatics, fluorescence microscopy, and CRISPR-based functional assays [1, 2, 4, 5, 7].
What diseases are linked to intermediate filament-based processes?
They are linked to genetic skin disorders like epidermolytic palmoplantar keratoderma, cancer progression [4, 5], and metabolic/reproductive disorders.
What is the role of KRT6C in intermediate filament-based process?
KRT6C is a keratin that forms heterodimers with KRT9, and mutations are associated with cutaneous disorders.
How does CRISPR help study intermediate filament-based process?
CRISPR enables knockout, point mutation, knock-in, and overexpression of intermediate filament genes to dissect their functions in cellular models.
What methods identify intermediate filament interaction partners?
Proteomic profiling, such as that used to identify KRT6C as a partner for KRT9, is a key method.
Is intermediate filament-based process involved in cancer?
Yes, aberrant expression of intermediate filament genes is observed in breast ductal carcinoma in situ progression and colorectal cancer.
What model systems are used for intermediate filament research?
Cell lines, animal models (e.g., rats for erectile dysfunction), and CRISPR-edited cells are commonly used.
How can I create a knockout of an intermediate filament gene?
EDITGENE provides custom CRISPR knockout services for intermediate filament genes in your cell type of interest.
Conclusion
GO:0045103, intermediate filament-based process, encompasses the dynamic and essential roles of intermediate filaments in cellular mechanics, signaling, and disease. Research has linked these processes to genetic skin disorders, cancer progression, and metabolic conditions, underscoring their broad biomedical relevance [2, 4, 5, 7]. Advanced methodologies, including proteomics, high-throughput sequencing, and CRISPR-based editing, are crucial for unraveling the molecular mechanisms and identifying therapeutic targets. Continued investigation of intermediate filament-based processes promises to yield new insights into human health and disease.
References
- 1. Mamalakis M et al.. 2024. A novel pipeline employing deep multi-attention channels network for the autonomous detection of metastasizing cells through fluorescence microscopy.. Comput Biol Med 181:109052 PMID: 39216406
- 2. Li P et al.. 2023. Proteomic profiling reveals KRT6C as a probable hereterodimer partner for KRT9: New insights into re-classifying epidermolytic palmoplantar keratoderma (EPPK) and a milder form of pachyonychia congenita (PC-K6c) as a group of genetic cutaneous disorders.. J Proteomics 287:104971 PMID: 37467889
- 3. Wang J et al.. 2021. Genome-wide identification and characterization of perirenal adipose tissue microRNAs in rabbits fed a high-fat diet.. Biosci Rep 41(4) PMID: 33851695
- 4. Zhang J et al.. 2021. The possible role of SRMS in colorectal cancer by bioinformatics analysis.. World J Surg Oncol 19(1):326 PMID: 34781983
- 5. Song G et al.. 2020. Identification of aberrant gene expression during breast ductal carcinoma in situ progression to invasive ductal carcinoma.. J Int Med Res 48(1):300060518815364 PMID: 30712460
- 6. Taye M et al.. 2017. Whole genome scan reveals the genetic signature of African Ankole cattle breed and potential for higher quality beef.. BMC Genet 18(1):11 PMID: 28183280
- 7. Kang JQ et al.. 2021. Identification of key genes in type 2 diabetes-induced erectile dysfunction rats with stem cell therapy through high-throughput sequencing and bioinformatic analysis.. Andrologia 53(5):e14031 PMID: 33756037
