GO:0031005 filamin binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031005 filamin binding is a molecular function describing the selective binding of a protein to any filamin family member (filamin A, B, or C), which are large actin-crosslinking cytoskeletal proteins.
• Filamins contain an N-terminal actin-binding domain followed by a rod domain of immunoglobulin-like repeats and a C-terminal dimerization domain, enabling them to crosslink actin filaments into networks and stress fibers.
• Filamin binding partners include membrane receptors, signaling scaffolds, and structural proteins, and these interactions regulate cell adhesion, migration, and mechanotransduction.
• Mutations in FLNC, the gene encoding filamin C, cause cardiomyopathies and myopathies, highlighting the clinical importance of filamin interactions in muscle tissue.
• Filamin A binds pro-prion protein, and this interaction has been implicated in cancer cell biology, suggesting filamin binding is relevant to oncology.
• Experimental approaches to study filamin binding include AlphaFold2-based computational screening, co-immunoprecipitation, and CRISPR-engineered cell models.
Description
Filamin binding (GO:0031005) is a molecular function defined as the binding to a filamin, any member of a family of high molecular mass cytoskeletal proteins that crosslink actin filaments to form networks and stress fibers. Filamins are among the most abundant actin-binding proteins in mammalian cells and serve as scaffolds for numerous signaling and structural proteins. The term encompasses binding to all filamin isoforms, including filamin A (ABP-280), filamin B (ABP-278/276), and filamin C (ABPL), which are encoded by distinct genes but share a conserved domain architecture. Understanding filamin binding is critical because these interactions influence cell shape, motility, mechanosensing, and tissue integrity. Research on filamin binding has expanded from basic cytoskeletal biology to disease mechanisms. For example, filamin C mutations are linked to cardiomyopathies and myopathies, and filamin B regulates endothelial receptor retention. Filamin A interacts with pro-prion protein, implicating filamin binding in cancer. Computational and biochemical methods, such as AlphaFold2 screening and co-immunoprecipitation, are now used to identify and characterize filamin-binding proteins. This article provides a research-grade overview of GO:0031005, covering its definition, mechanism, key genes, disease relevance, and experimental models.
filamin binding At A Glance
| GO ID | GO:0031005 |
|---|---|
| GO term | filamin binding |
| Ontology | molecular_function |
| Synonym | ABP-278/276 binding, ABP-280 binding, ABPL binding, alpha-filamin binding, beta-filamin binding, filamin-1 binding, filamin-2 binding, filamin-3 binding, filamin A binding, filamin-A binding, filamin B binding, filamin-B binding, filamin C binding, filamin-C binding, gamma-filamin binding |
| Major function | Binding to a filamin family member, which crosslinks actin filaments into networks and stress fibers |
| Domain architecture of filamins | N-terminal alpha-actinin-like actin-binding domain; rod domain of 4-24 100-residue repeats; C-terminal dimerization domain |
| Major isoforms | Filamin A (ABP-280), filamin B (ABP-278/276), filamin C (ABPL) |
| Related diseases | Cardiomyopathy, myopathy, cancer, and other conditions linked to filamin mutations or interactions |
What Is GO:0031005?
In our own words, GO:0031005 filamin binding describes the function of a protein that selectively binds to a filamin family member. Filamins are large cytoskeletal proteins that crosslink actin filaments into networks and stress fibers. They contain an amino-terminal alpha-actinin-like actin-binding domain, a rod domain composed of 4 to 24 repetitive segments of about 100 residues each, and a carboxy-terminal dimerization domain. This molecular function is attributed to proteins that physically interact with any filamin isoform, including filamin A, B, or C, and it is distinct from actin binding itself because the target is the filamin protein, not actin.
Why Is filamin binding Important in Cell Biology?
Filamin binding is important because filamins are central organizers of the actin cytoskeleton and participate in diverse cellular processes, including cell migration, adhesion, and mechanotransduction. Proteins that bind filamins can modulate these processes, and disruptions in filamin interactions are associated with human diseases such as cardiomyopathies, myopathies, and cancer. Studying GO:0031005 helps researchers understand how cells integrate mechanical and biochemical signals and how mutations in filamin or its binding partners lead to pathology.
• Filamin binding regulates actin cytoskeleton organization and cell shape.
• It is involved in mechanotransduction and cellular responses to mechanical stress.
• Filamin A binding to pro-prion protein has been implicated in cancer biology.
• Filamin B binding regulates endothelial sphingosine 1-phosphate receptor 1 cell-surface retention.
• Filamin C mutations are linked to cardiomyopathies and myopathies.
• Filamin interactions with titin and other Z-disc proteins are essential for muscle sarcomere integrity.
• Filamin binding proteins can serve as therapeutic targets or biomarkers in disease.
• Computational tools like AlphaFold2 enable prediction of filamin-binding interfaces.
• CRISPR-based models allow functional dissection of filamin-binding domains.
• Understanding filamin binding can inform tissue engineering and regenerative medicine.
Molecular Mechanism of filamin binding
Filamin domain architecture and actin crosslinking
In simple terms: Filamins are long, flexible proteins that grab actin filaments and hold them together in networks.
Filamins are high molecular mass cytoskeletal proteins that crosslink actin filaments to form networks and stress fibers. They contain an amino-terminal alpha-actinin-like actin-binding domain, which is followed by a rod domain composed of 4 to 24 100-residue repetitive segments including a carboxy-terminal dimerization domain. This architecture allows filamins to dimerize and bind multiple actin filaments, creating a crosslinked cytoskeletal meshwork.
Binding interfaces and partner recognition
In simple terms: Proteins that bind filamin do so by recognizing specific regions on the filamin molecule.
Filamin-binding proteins interact with various domains of filamins, often through the immunoglobulin-like repeats in the rod domain or the C-terminal region. For example, filamin B regulates the cell-surface retention of endothelial sphingosine 1-phosphate receptor 1 through direct binding. Filamin A binds pro-prion protein, and this interaction has been structurally and functionally characterized. Computational screening using AlphaFold2 has been used to predict mechanical binding proteins of filamin, highlighting the importance of structural complementarity.
Regulation by mechanical force and signaling
In simple terms: Filamin binding can be strengthened or weakened by forces and signals inside the cell.
Filamins are mechanosensitive proteins, and their binding interactions can be modulated by mechanical force. For instance, filamin C in the muscle Z-disc interacts with titin and other proteins to maintain sarcomere integrity, and these interactions are critical for responding to mechanical stress. Signaling pathways can also regulate filamin binding; for example, phosphorylation of filamin or its partners may alter binding affinity.
Functional consequences of filamin binding
In simple terms: When a protein binds filamin, it can change how cells move, stick, or respond to their environment.
Filamin binding can influence cell migration, adhesion, and signaling. Filamin B binding to sphingosine 1-phosphate receptor 1 affects receptor retention at the cell surface, thereby modulating endothelial barrier function. Filamin A binding to pro-prion protein has been implicated in cancer cell proliferation and survival. In muscle, filamin C interactions with titin and other Z-disc proteins are essential for maintaining sarcomere cohesion and function.
Filamin binding in disease and co-aggregation
In simple terms: Abnormal filamin binding can contribute to diseases, including neurodegeneration and muscle disorders.
Mutations in FLNC, encoding filamin C, cause cardiomyopathies and myopathies, often by disrupting interactions with binding partners. In neurodegeneration, TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins, including filamins, suggesting a role for filamin binding in protein aggregation pathologies. These findings underscore the importance of understanding filamin binding in both structural and degenerative diseases.
Key Genes Involved in GO:0031005 filamin binding
The following genes encode filamins or well-characterized filamin-binding proteins that are central to GO:0031005 research.
| Gene | Major Role | Research Relevance |
|---|---|---|
| FLNA | Encodes filamin A (ABP-280), an actin-crosslinking protein | Binds pro-prion and other partners; implicated in cancer and developmental disorders |
| FLNB | Encodes filamin B (ABP-278/276), an actin-crosslinking protein | Regulates endothelial receptor retention; linked to skeletal disorders |
| FLNC | Encodes filamin C (ABPL), a muscle-specific filamin | Mutations cause cardiomyopathies and myopathies |
| PRNP | Encodes prion protein; pro-prion binds filamin A | Interaction with filamin A implicated in cancer |
| S1PR1 | Encodes sphingosine 1-phosphate receptor 1 | Cell-surface retention regulated by filamin B binding |
| TTN | Encodes titin, a giant sarcomere protein | Interacts with filamin C in Z-disc cohesion |
| BAG3 | Encodes BAG3, a co-chaperone | Guides co-aggregation with actin-binding proteins including filamins |
| HSPA1A | Encodes HSP70, a molecular chaperone | Participates in co-aggregation with filamins in neurodegeneration |
| ACTN2 | Encodes alpha-actinin-2, a Z-disc protein | Shares actin-binding domain homology with filamins |
| VCL | Encodes vinculin, a focal adhesion protein | Potential filamin-binding partner in mechanotransduction |
| ITGB1 | Encodes integrin beta-1 | Links to filamin-associated adhesion complexes |
| TLN1 | Encodes talin-1, an integrin adaptor | May compete or cooperate with filamin binding |
| MYH9 | Encodes myosin heavy chain 9 | Cytoskeletal motor that interacts with filamin networks |
| ACTB | Encodes beta-actin | Filamin crosslinks actin filaments; actin is the substrate |
| ACTG1 | Encodes gamma-actin | Filamin crosslinks actin filaments in stress fibers |
| DMD | Encodes dystrophin | Muscle cytoskeletal protein that may interact with filamin C |
| SGCD | Encodes delta-sarcoglycan | Muscle membrane protein in dystrophin complex |
| LDB3 | Encodes LIM domain-binding 3 (ZASP) | Z-disc protein that interacts with filamin C |
How Is filamin binding Regulated?
Filamin binding is regulated at multiple levels. Mechanical force can alter filamin conformation and expose or hide binding sites, thereby modulating interactions with partners. Phosphorylation of filamins or their binding partners can affect binding affinity and complex stability. In muscle, filamin C interactions with titin and other Z-disc proteins are regulated during sarcomere assembly and maintenance. Additionally, co-chaperones such as BAG3 and HSP70 can guide co-aggregation of filamins with other proteins under stress conditions, influencing filamin binding in disease contexts.
filamin binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| FLNC | Cardiomyopathy, myopathy | Knockout or point-mutation knock-in in cardiomyocytes |
| FLNA | Cancer, developmental disorders | Overexpression or knockout in cancer cell lines |
| FLNB | Vascular barrier dysfunction | Endothelial cell knockout or knock-in |
| PRNP | Cancer | Point mutation of filamin-binding domain in cancer cells |
| BAG3 | Neurodegeneration | Knockout or tagged knock-in in neuronal cells |
Filamin binding in cardiomyopathies and myopathies
Mutations in FLNC, which encodes filamin C, are associated with cardiomyopathies and myopathies. These mutations often disrupt filamin C interactions with titin and other Z-disc proteins, leading to impaired sarcomere cohesion and muscle dysfunction. Understanding filamin binding is therefore critical for elucidating the molecular basis of these diseases and for developing targeted therapies.
Filamin binding in cancer
Filamin A binds pro-prion protein, and this interaction has been implicated in cancer cell biology. The binding of pro-prion to filamin A may affect cell adhesion, migration, and survival, contributing to tumor progression. Targeting filamin-binding interfaces could offer novel therapeutic strategies in oncology.
Filamin binding in neurodegeneration
TDP-43 skein-like inclusions, a hallmark of certain neurodegenerative diseases, are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins, including filamins. This suggests that filamin binding may play a role in protein aggregation pathologies, and modulating these interactions could be a therapeutic avenue.
Filamin binding in vascular biology
Filamin B regulates the cell-surface retention of endothelial sphingosine 1-phosphate receptor 1, which is important for endothelial barrier function. Disruption of this interaction may contribute to vascular leak and inflammation, making filamin binding a potential target for vascular diseases.
From filamin binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of filamin binding affect actin cytoskeleton? | FLNA/B/C knockout cell lines |
| Does a specific filamin mutation alter binding affinity? | Point-mutation knock-in of FLNC or FLNA |
| Can a filamin-binding domain be tagged for imaging? | Tagged knock-in of filamin or partner |
| Does overexpression of a filamin-binding protein drive disease? | Overexpression cell models |
| Which proteins bind filamin under mechanical stress? | AlphaFold2 screening and co-immunoprecipitation |
| Does filamin binding regulate receptor retention? | Endothelial cells with FLNB knockout |
How to Study the filamin binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| AlphaFold2 screening | Predicted binding interfaces | Identify novel filamin-binding proteins |
| Co-immunoprecipitation | Physical interaction | Validate filamin binding in cell lysates |
| Pull-down assay | Direct binding | Test recombinant filamin domains |
| Fluorescence microscopy | Subcellular localization | Visualize filamin and partners |
| CRISPR knockout | Loss of function | Assess filamin binding requirement |
| Point-mutation knock-in | Specific residue function | Dissect binding interface |
| Overexpression | Gain of function | Model disease-associated binding |
| Proteomics | Interaction network | Identify filamin-associated proteins |
Computational prediction of filamin-binding proteins
AlphaFold2-based computational screening has been used to identify mechanical binding proteins of filamin, providing structural insights into binding interfaces. This approach can prioritize candidate interactors for experimental validation.
Biochemical assays for filamin binding
Co-immunoprecipitation, pull-down assays, and surface plasmon resonance can detect and quantify filamin binding. These methods are essential for confirming interactions predicted computationally or identified in screens.
Cell biology and imaging
Fluorescence microscopy and live-cell imaging can visualize filamin localization and dynamics in actin networks. Tagged knock-in models allow tracking of filamin-binding proteins in real time.
CRISPR-based functional studies
CRISPR knockout, point mutation, and knock-in models enable functional dissection of filamin-binding domains and their roles in disease. These models are critical for linking binding events to cellular phenotypes.
How CRISPR Can Be Used to Study GO:0031005 filamin binding
Knockout
CRISPR knockout of FLNA, FLNB, or FLNC can abolish filamin binding and reveal its role in cytoskeletal organization and disease. Knockout cell lines are valuable for studying loss-of-function phenotypes.
Point Mutation
Point-mutation knock-in of specific residues in filamin or its binding partners can disrupt binding interfaces while preserving protein expression, allowing precise structure-function studies.
Knock-in
Tagged knock-in of filamins or their partners enables imaging and biochemical tracking of filamin binding in live cells. This approach is useful for dynamic studies of interaction.
Overexpression
Overexpression of filamin-binding proteins can model gain-of-function effects observed in cancer and other diseases. This approach helps identify downstream signaling changes.
How EDITGENE Supports filamin binding Research
Researchers studying filamin binding-related genes often need to determine whether a candidate gene is causally involved in cytoskeletal regulation or disease. EDITGENE provides CRISPR-based cell models and screening services to accelerate this discovery process.
Contact EDITGENE today to design your custom CRISPR model for filamin binding research.
Frequently Asked Questions About filamin binding
What is filamin binding?
Filamin binding (GO:0031005) is a molecular function describing the binding to a filamin, a large actin-crosslinking cytoskeletal protein.
What genes are involved in filamin binding?
Key genes include FLNA, FLNB, and FLNC, which encode filamin A, B, and C, respectively, as well as binding partners like PRNP and S1PR1.
What diseases are associated with filamin binding?
Filamin binding is linked to cardiomyopathies, myopathies, cancer, neurodegeneration, and vascular disorders.
How is filamin binding studied?
Methods include AlphaFold2 screening, co-immunoprecipitation, fluorescence microscopy, and CRISPR-based models.
What is the role of filamin C in muscle?
Filamin C interacts with titin and other Z-disc proteins to maintain sarcomere integrity, and mutations cause muscle diseases.
Does filamin A bind pro-prion protein?
Yes, filamin A binds pro-prion protein, and this interaction has been implicated in cancer.
How does filamin B regulate endothelial receptors?
Filamin B binds sphingosine 1-phosphate receptor 1 and regulates its cell-surface retention.
Can CRISPR be used to study filamin binding?
Yes, CRISPR knockout, point mutation, and knock-in models are used to dissect filamin-binding functions.
What is the domain structure of filamins?
Filamins have an N-terminal actin-binding domain, a rod domain of 4-24 repeats, and a C-terminal dimerization domain.
Why is filamin binding important for cell migration?
Filamin binding regulates actin cytoskeleton dynamics, which is essential for cell migration and adhesion.
Conclusion
GO:0031005 filamin binding is a fundamental molecular function that governs actin cytoskeleton organization, mechanotransduction, and cell signaling. Filamins A, B, and C interact with diverse partners, and disruptions in these interactions are linked to cardiomyopathies, myopathies, cancer, and neurodegeneration. Advances in computational prediction and CRISPR-based models are accelerating our understanding of filamin binding in health and disease. Continued research will likely uncover new therapeutic opportunities targeting filamin interactions.
References
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- 2. Verdonschot JAJ et al.. 2020. A mutation update for the FLNC gene in myopathies and cardiomyopathies.. Hum Mutat 41(6):1091-1111 PMID: 32112656
- 3. Johnson J et al.. 2025. Computational screening of filamin mechanical binding proteins using AlphaFold2.. Biochem Cell Biol 103:1-11 PMID: 40773774
- 4. Zhao X et al.. 2023. Actin-binding protein filamin B regulates the cell-surface retention of endothelial sphingosine 1-phosphate receptor 1.. J Biol Chem 299(7):104851 PMID: 37220855
- 5. González-Morales N et al.. 2017. Filamin actin-binding and titin-binding fulfill distinct functions in Z-disc cohesion.. PLoS Genet 13(7):e1006880 PMID: 28732005
- 6. Li C et al.. 2010. Binding of pro-prion to filamin A: by design or an unfortunate blunder.. Oncogene 29(39):5329-45 PMID: 20697352
- 7. Lu S et al.. 2025. TDP-43 skein-like inclusions are formed by BAG3- and HSP70-guided co-aggregation with actin-binding proteins.. Nat Cell Biol 27(11):1925-1937 PMID: 41174004
- 8. Mao Z et al.. 2020. Structure and Function of Filamin C in the Muscle Z-Disc.. Int J Mol Sci 21(8) PMID: 32295012
