GO:0032051 clathrin light chain binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0032051 (clathrin light chain binding) is a molecular function defined as binding to a clathrin light chain, a regulatory subunit of the clathrin coat.
• Clathrin light chains (CLTA, CLTB) modulate clathrin-coated pit dynamics, cargo selection, and recruitment of accessory proteins such as myosin VI.
• Clathrin light chain interactions are implicated in cancer progression, including hepatocellular carcinoma, where CLCB drives angiogenesis and NF-kB signaling.
• Clathrin light chain-conjugated drug delivery systems are being explored for targeted cancer therapy.
• Clathrin light chain binding is linked to autophagy through interactions with ATG8 proteins, connecting endocytosis and autophagic pathways.
• Research tools such as knockout, knock-in, and overexpression models are essential to dissect the functional roles of clathrin light chain binding in health and disease.
Description
Clathrin light chain binding (GO:0032051) is a molecular function that describes the physical interaction between a protein and a clathrin light chain (CLC) subunit. Clathrin light chains are regulatory components of the clathrin triskelion, which forms the coat around vesicles during clathrin-mediated endocytosis. This binding event is critical for recruiting accessory proteins, modulating coat assembly, and coordinating membrane trafficking. Understanding this function is essential because clathrin light chains influence cargo selection, vesicle scission, and signaling pathways that are often dysregulated in cancer and other diseases. Researchers study clathrin light chain binding to uncover how cells control endocytosis, autophagy, and receptor downregulation, and to develop targeted therapeutics.
clathrin light chain binding At A Glance
| GO ID | GO:0032051 |
|---|---|
| GO term | clathrin light chain binding |
| Ontology | molecular_function |
| Synonym | none |
| Major function | Binding to a clathrin light chain, regulating clathrin-coated vesicle formation and cargo recruitment. |
| Related cellular component | clathrin-coated pit, clathrin-coated vesicle |
| Related biological process | clathrin-mediated endocytosis, autophagy |
| Example binding partners | CLTA, CLTB, myosin VI, ATG8 proteins |
What Is GO:0032051?
GO:0032051, clathrin light chain binding, is defined as the selective interaction of a protein or molecule with a clathrin light chain. Clathrin light chains are small subunits that associate with clathrin heavy chains to form the clathrin lattice. This binding function is distinct from binding to clathrin heavy chains and often involves regulatory proteins that modulate clathrin-coated pit dynamics.
Why Is clathrin light chain binding Important in Cell Biology?
Clathrin light chain binding is important because it governs the recruitment of regulatory proteins to clathrin-coated pits, thereby influencing endocytosis, receptor signaling, and membrane remodeling. Dysregulation of this function has been linked to cancer progression, where clathrin light chain B (CLCB) promotes angiogenesis and NF-kB signaling in hepatocellular carcinoma. Moreover, clathrin light chain interactions with myosin VI are required for selective cargo uptake under membrane tension, and with ATG8 proteins they connect endocytosis to autophagy. Thus, understanding this molecular function provides insights into fundamental cell biology and potential therapeutic targets.
• Regulates clathrin-coated pit assembly and dynamics.
• Modulates cargo selection and vesicle scission.
• Implicated in cancer progression, including hepatocellular carcinoma.
• Enables targeted drug delivery via clathrin light chain conjugation.
• Links endocytosis to autophagy through ATG8 interactions.
• Influences receptor signaling, such as alpha1-adrenoceptors in prostate.
• Provides selectivity among adaptor proteins in budding yeast.
• Potential target for therapeutic intervention in cancer and other diseases.
What Happens During clathrin light chain binding?
Recruitment of clathrin light chains to coated pits
In simple terms: Clathrin light chains attach to the clathrin coat at the cell membrane.
Clathrin light chains (CLTA and CLTB) bind to clathrin heavy chains and are incorporated into the clathrin triskelion. This binding is essential for the structural integrity of the coat and for recruiting other proteins. For example, noradrenaline induces binding of clathrin light chain A to alpha1-adrenoceptors in the human prostate, suggesting a role in receptor internalization.
Interaction with myosin VI under membrane tension
In simple terms: Clathrin light chain A helps pull the vesicle inward using myosin VI.
Clathrin light chain A drives selective recruitment of myosin VI to clathrin-coated pits, particularly under membrane tension. This interaction is critical for efficient endocytosis and cargo sorting.
Connection to autophagy via ATG8 proteins
In simple terms: Clathrin light chains can interact with autophagy proteins to link endocytosis and autophagy.
CLC2 (clathrin light chain 2) interacts with ATG8h/ATG8i, connecting clathrin-mediated endocytosis to the autophagy pathway. This crosstalk is important for cellular homeostasis and stress responses.
Selectivity among adaptor proteins
In simple terms: Clathrin light chains help choose which adaptor proteins bind to the coat.
Subtleties in clathrin heavy chain binding boxes provide selectivity among adaptor proteins in budding yeast, indicating that clathrin light chain binding contributes to the specificity of cargo recruitment.
Key Genes Involved in GO:0032051 clathrin light chain binding
The following genes and proteins are directly involved in clathrin light chain binding and its related processes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| CLTA | Clathrin light chain A; binds to clathrin heavy chain and regulatory proteins | Studied for its role in endocytosis, receptor internalization, and cancer |
| CLTB | Clathrin light chain B; regulates clathrin coat assembly | Implicated in hepatocellular carcinoma progression and angiogenesis |
| MYO6 | Myosin VI; motor protein recruited by CLTA | Required for selective endocytosis under membrane tension |
| ATG8H | Autophagy-related protein; interacts with CLC2 | Links endocytosis to autophagy |
| ATG8I | Autophagy-related protein; interacts with CLC2 | Links endocytosis to autophagy |
| AP2M1 | Adaptor protein complex 2 subunit mu; mediates endocytosis | Involved in autophagy-induced CLDN2 degradation |
| CLDN2 | Claudin 2; tight junction protein | Degraded via AP2M1-mediated endocytosis |
| LC3 | Autophagy marker; interacts with AP2M1 | Connects endocytosis and autophagy |
| ADRA1A | Alpha1-adrenoceptor; binds CLTA | Studied in prostate physiology |
| AP180 | Adaptor protein; binds clathrin | Involved in clathrin-mediated endocytosis |
| AUXILIN | Auxilin; binds clathrin | Role in uncoating |
| CLTC | Clathrin heavy chain; forms triskelion with light chains | Central to clathrin-coated vesicle formation |
| NFKB1 | NF-kB subunit; downstream of CLCB signaling | Linked to hepatocellular carcinoma progression |
| PCLAF | PCNA clamp associated factor; involved in NF-kB pathway | Part of CLCB-driven signaling axis |
| VEGFA | Vascular endothelial growth factor A; angiogenesis | Induced by CLCB in small extracellular vesicles |
| RAB5 | Early endosome marker; regulates endocytosis | General endocytic pathway component |
| EPS15 | EGFR pathway substrate 15; endocytic adaptor | Involved in clathrin-mediated endocytosis |
| DNM2 | Dynamin 2; mediates vesicle scission | Works with clathrin light chains in endocytosis |
How Is clathrin light chain binding Regulated?
Clathrin light chain binding is regulated by various factors, including membrane tension, which enhances the recruitment of myosin VI by clathrin light chain A. Noradrenaline stimulates the binding of clathrin light chain A to alpha1-adrenoceptors, indicating hormonal regulation. Additionally, interactions with ATG8 proteins link clathrin light chain function to autophagy, which is regulated by nutrient status and stress. The NF-kB pathway can be modulated by clathrin light chain B signaling, suggesting feedback regulation in cancer cells.
clathrin light chain binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| CLTB | Hepatocellular carcinoma | Knockout or overexpression in liver cancer cell lines |
| CLTA | Prostate physiology | Knockout in prostate cell lines |
| AP2M1 | Intestinal barrier dysfunction | Knockout in intestinal epithelial cells |
| CLTA/CLTB | Cancer drug delivery | Conjugation to nanoparticles for targeted therapy |
| ATG8H/ATG8I | Autophagy-related diseases | Knockout in autophagy reporter cells |
Clathrin light chain binding in cancer
Clathrin light chain B (CLCB) drives hepatocellular carcinoma progression through dual mechanisms: small extracellular vesicle-mediated angiogenesis and the NF-kB-PCLAF signaling axis. This highlights the oncogenic potential of clathrin light chain interactions. Additionally, clathrin light chain-conjugated drug delivery systems are being developed for cancer therapy, exploiting the binding properties of clathrin light chains.
Clathrin light chain binding in autophagy and intestinal barrier
AP2M1 mediates autophagy-induced CLDN2 degradation through endocytosis and interaction with LC3, reducing intestinal epithelial tight junction permeability. This links clathrin-mediated endocytosis to autophagy and gut barrier function. Similarly, CLC2 interactions with ATG8 proteins connect endocytosis to autophagy, with implications for cellular homeostasis.
Clathrin light chain binding in prostate physiology
Noradrenaline induces binding of clathrin light chain A to alpha1-adrenoceptors in the human prostate, suggesting a role in receptor regulation and prostate function.
From clathrin light chain binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does CLTB knockout reduce tumor growth? | CLTB knockout hepatocellular carcinoma cell lines and mouse xenografts |
| How does CLTA point mutation affect myosin VI recruitment? | Point-mutation knock-in of CLTA in epithelial cells |
| Can clathrin light chain binding be used for drug delivery? | Knock-in of tagged CLTA for conjugation studies |
| What is the role of CLC2 in autophagy? | Overexpression of CLC2 and ATG8 mutants in mammalian cells |
| How does AP2M1 regulate CLDN2 degradation? | AP2M1 knockout intestinal epithelial cells |
| Does noradrenaline regulate CLTA binding? | Overexpression of CLTA in prostate cells treated with noradrenaline |
How to Study the clathrin light chain binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Co-immunoprecipitation | Protein-protein interactions | Identifying clathrin light chain binding partners |
| Mass spectrometry | Proteomic composition of complexes | Discovering novel interactors |
| TIRF microscopy | Real-time dynamics of clathrin-coated pits | Studying recruitment of myosin VI |
| CRISPR knockout | Loss-of-function phenotypes | Assessing role in cancer progression |
| RNA-seq | Transcriptional changes | Evaluating NF-kB signaling upon CLCB modulation |
| Western blot | Protein expression and degradation | Measuring CLDN2 degradation |
| GST pull-down | Direct binding | Mapping clathrin light chain interaction domains |
| Autophagy flux assay | Autophagic activity | Linking CLC2 to autophagy |
Proteomic analysis of clathrin light chain interactions
Affinity purification coupled with mass spectrometry can identify proteins that bind to clathrin light chains. This approach has been used to uncover interactions with myosin VI and ATG8 proteins.
Live-cell imaging of clathrin-coated pits
Total internal reflection fluorescence (TIRF) microscopy allows visualization of clathrin light chain dynamics and recruitment of accessory proteins in real time.
Genetic knockout and knockdown
CRISPR-Cas9 knockout or siRNA knockdown of CLTA and CLTB can reveal their roles in endocytosis, autophagy, and cancer progression.
Biochemical binding assays
In vitro binding assays, such as GST pull-down or surface plasmon resonance, can measure direct interactions between clathrin light chains and partner proteins.
How CRISPR Can Be Used to Study GO:0032051 clathrin light chain binding
Knockout
CRISPR-Cas9 knockout of CLTA or CLTB can abolish clathrin light chain binding, leading to defects in endocytosis and autophagy. For example, CLTB knockout reduces hepatocellular carcinoma progression in xenograft models.
Point Mutation
Introducing point mutations in clathrin light chain binding interfaces can disrupt specific interactions, such as the binding of CLTA to myosin VI, without affecting overall clathrin assembly.
Knock-in
Knock-in of tagged clathrin light chains (e.g., GFP or HA) allows visualization and affinity purification of binding complexes in live cells.
Overexpression
Overexpression of CLTB or CLTA can enhance clathrin light chain binding and downstream signaling, such as NF-kB activation in cancer cells.
How EDITGENE Supports clathrin light chain binding Research
Researchers studying clathrin light chain binding-related genes often need to determine whether a candidate gene is causally involved in endocytosis, autophagy, or cancer progression. EDITGENE provides comprehensive CRISPR-based services to create precise cellular models for such investigations.
Contact EDITGENE today to design your custom CRISPR model for clathrin light chain binding research.
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CLTCL1 Knockout HEK293 Cell Line | EDJ-KQ2806 | Human | 8218 | Details Get a Quote |
| HIP1 Knockout HEK293 Cell Line | EDJ-KQ4867 | Human | 3092 | Details Get a Quote |
| HIP1R Knockout HEK293 Cell Line | EDJ-KQ5753 | Human | 9026 | Details Get a Quote |
| NSG1 Knockout HEK293 Cell Line | EDJ-KQ8660 | Human | 27065 | Details Get a Quote |
| CALY Knockout HEK293 Cell Line | EDJ-KQ10789 | Human | 50632 | Details Get a Quote |
| NSG2 Knockout HEK293 Cell Line | EDJ-KQ11160 | Human | 51617 | Details Get a Quote |
| CLTCL1 Knockout HeLa Cell Line | EDJ-KQ22383 | Human | 8218 | Details Get a Quote |
| CLTCL1 Knockout A-549 Cell Line | EDJ-KQ23749 | Human | 8218 | Details Get a Quote |
| CLTCL1 Knockout HCT 116 Cell Line | EDJ-KQ23750 | Human | 8218 | Details Get a Quote |
| HIP1 Knockout A-549 Cell Line | EDJ-KQ27645 | Human | 3092 | Details Get a Quote |
| HIP1 Knockout HCT 116 Cell Line | EDJ-KQ27646 | Human | 3092 | Details Get a Quote |
| HIP1 Knockout HeLa Cell Line | EDJ-KQ27647 | Human | 3092 | Details Get a Quote |
| HIP1R Knockout A-549 Cell Line | EDJ-KQ30495 | Human | 9026 | Details Get a Quote |
| HIP1R Knockout HCT 116 Cell Line | EDJ-KQ30497 | Human | 9026 | Details Get a Quote |
| HIP1R Knockout HeLa Cell Line | EDJ-KQ30498 | Human | 9026 | Details Get a Quote |
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Frequently Asked Questions About clathrin light chain binding
What is clathrin light chain binding?
Clathrin light chain binding (GO:0032051) is a molecular function where a protein binds to a clathrin light chain, regulating clathrin-coated vesicle formation and cargo recruitment.
What genes are involved in clathrin light chain binding?
Key genes include CLTA and CLTB, which encode clathrin light chains, as well as MYO6, ATG8H, ATG8I, and AP2M1.
How does clathrin light chain binding affect cancer?
CLCB drives hepatocellular carcinoma progression through angiogenesis and NF-kB signaling, making it a potential therapeutic target.
What is the role of clathrin light chain A in endocytosis?
CLTA recruits myosin VI to clathrin-coated pits under membrane tension, facilitating selective cargo uptake.
Can clathrin light chain binding be targeted for drug delivery?
Yes, clathrin light chain-conjugated drug delivery systems are being developed for cancer therapy.
How is clathrin light chain binding linked to autophagy?
CLC2 interacts with ATG8 proteins, connecting clathrin-mediated endocytosis to autophagy.
What experimental models are used to study clathrin light chain binding?
Knockout, point mutation, knock-in, and overexpression cell models, as well as animal xenografts, are commonly used.
What methods detect clathrin light chain binding?
Co-immunoprecipitation, mass spectrometry, TIRF microscopy, and GST pull-down are standard methods.
Is clathrin light chain binding involved in prostate function?
Noradrenaline induces CLTA binding to alpha1-adrenoceptors in the human prostate, suggesting a regulatory role.
How does AP2M1 relate to clathrin light chain binding?
AP2M1 mediates autophagy-induced CLDN2 degradation through endocytosis, linking clathrin function to intestinal barrier regulation.
Conclusion
Clathrin light chain binding (GO:0032051) is a fundamental molecular function that orchestrates clathrin-coated vesicle dynamics, cargo selection, and crosstalk with autophagy. Its dysregulation is implicated in cancer progression and other diseases, making it a compelling target for therapeutic development. Advanced CRISPR models and biochemical assays continue to unravel the precise mechanisms and regulatory networks governed by clathrin light chain interactions.
References
- 1. Sun X et al.. 2025. Clathrin Light Chain B Drives Hepatocellular Carcinoma Progression Through Dual Mechanisms: Small Extracellular Vesicle-Mediated Angiogenesis and the NF-κB-PCLAF Signaling Axis.. Adv Sci (Weinh) 12(42):e08613 PMID: 40820941
- 2. Jung S et al.. 2023. Clathrin light chain-conjugated drug delivery for cancer.. Bioeng Transl Med 8(1):e10273 PMID: 36684105
- 3. Defelipe LA et al.. 2024. Subtleties in Clathrin heavy chain binding boxes provide selectivity among adaptor proteins of budding yeast.. Nat Commun 15(1):9655 PMID: 39511183
- 4. Hennenberg M et al.. 2013. Noradrenaline induces binding of Clathrin light chain A to α1-adrenoceptors in the human prostate.. Prostate 73(7):715-23 PMID: 23460120
- 5. Biancospino M et al.. 2019. Clathrin light chain A drives selective myosin VI recruitment to clathrin-coated pits under membrane tension.. Nat Commun 10(1):4974 PMID: 31672988
- 6. Lan H et al.. 2025. CLC2 (Clathrin Light Chain 2)-ATG8h/ATG8i interactions connect clathrin-mediated endocytosis (CME) and the autophagy pathway.. Autophagy 21(1):246-248 PMID: 39396122
- 7. Lindner R et al.. 1991. Light-chain-independent binding of adaptors, AP180, and auxilin to clathrin.. Biochemistry 30(37):9097-101 PMID: 1909890
- 8. Ganapathy AS et al.. 2022. AP2M1 mediates autophagy-induced CLDN2 (claudin 2) degradation through endocytosis and interaction with LC3 and reduces intestinal epithelial tight junction permeability.. Autophagy 18(9):2086-2103 PMID: 34964704
