FGF13 Human
Description
Molecular Structure and Isoforms
FGF13 exists in multiple isoforms due to alternative splicing, with the primary isoform (FGF13A) containing 245 amino acids and a molecular mass of 27.6 kDa . Key structural features include:
Isoform diversity allows FGF13 to interact with distinct cellular targets, such as voltage-gated sodium channels and microtubules .
Neuronal Development and Neuroprotection
FGF13 stabilizes microtubules, regulates neuronal polarization, and modulates axonal formation . In Alzheimer’s disease (AD) models:
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Cognitive Improvement: Overexpression reduces amyloid-β (Aβ) accumulation, tau phosphorylation, and oxidative stress .
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Mechanism: Activates PI3K/AKT/GSK-3β signaling, enhancing anti-apoptotic factors (BCL-2) and reducing pro-apoptotic markers (BAX, cleaved-caspase 3) .
| Parameter | Aβ-Induced Rats | FGF13-Overexpressed Rats |
|---|---|---|
| Cognitive Defects | ↑ (Morris water maze) | ↓ (Normal performance) |
| Oxidative Stress | ↑ ROS, ↓ GSH/SOD | ↓ ROS, ↑ GSH/SOD |
| Aβ Levels | ↑ | ↓ |
| Tau Phosphorylation | ↑ (Thr181/Ser404) | ↓ |
Data sourced from Aβ-induced rat models .
Cardiovascular Regulation
FGF13 modulates cardiac myocyte electrophysiology:
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Atrial Fibrillation (AF): Reduced FGF13 expression in left atrial cardiomyocytes correlates with postoperative AF vulnerability .
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Mechanism: Regulates late sodium currents (I_Na), preventing action potential duration (APD) prolongation .
Cancer Biology
FGF13 exhibits dual roles in oncology:
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Tumor Suppression: p53 inhibits FGF13 to suppress ribosomal RNA synthesis, limiting stress-induced cancer cell survival .
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Drug Resistance: Overexpression in cisplatin-resistant cells reduces intracellular platinum and copper, enhancing survival .
| Role | Mechanism | Outcome |
|---|---|---|
| Tumor Suppression | p53-mediated downregulation → ↓ ribosomal stress → ↑ cell death | Inhibit tumor growth |
| Drug Resistance | ↑ Copper/platinum efflux → ↓ intracellular drug concentrations | Enhance chemoresistance |
Neurodevelopmental Disorders
A 5′-UTR SNP (C>G) in FGF13 reduces protein translation, causing intellectual disability (ID) and epilepsy :
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Phenotypes: Severe ID, speech deficits, and autism spectrum traits in males .
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Mechanism: Impaired axonal branching and polarization in iPSC-derived neurons .
Cardiovascular Pathologies
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Hypertrophic Cardiomyopathy: FGF13 upregulation in nuclei of hypertrophic cardiomyocytes activates NF-κB, exacerbating fibrosis .
Neurodegenerative Diseases
FGF13 is downregulated in AD brains and rodent models, linking its deficiency to synapse loss and cognitive decline .
Research Findings and Therapeutic Potential
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AD Therapy: FGF13 overexpression rescues memory deficits in Aβ-injected rats, suggesting gene therapy potential .
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AF Prevention: Targeting FGF13 to stabilize late sodium currents may reduce postoperative AF risk .
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Cancer Targets: Inhibiting FGF13 in platinum-resistant tumors or activating it in p53-deficient cancers could improve outcomes .
Product Specs
Fibroblast growth factor 13 (FGF-13), a member of the extensive FGF family with over 23 members, is a binding growth factor. This family is characterized by a core 120 amino acid (aa) FGF domain, responsible for their shared tertiary structure. Human and mouse FGF13, consisting of 245 aa, are encoded by genes exhibiting alternative splicing at their N-termini. Several transcript variants have been observed in both species, encoding proteins of 245 aa, 199 aa, 226 aa, 192 aa, and 255 aa, with a high degree of cross-species amino acid identity (over 98%) across all isoforms. FGF13 expression is found in various tissues during fetal development, including the ependyma, dorsal root ganglia, cranial ganglia, both atrial and ventricular myocardium, and renal collecting duct-associated mesenchyme.
Q&A
FGF13 Human: Researcher-Focused FAQs
How do FGF13 expression patterns vary across tissues and disease states?
Experimental design considerations:
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Use isoform-specific antibodies (e.g., anti-FGF13-VY [Abcam ab12345]) for immunohistochemistry.
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Validate splice variants using 5’ RACE-PCR to resolve annotation discrepancies .
What experimental models are optimal for studying FGF13-related pathologies?
Advanced models:
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Conditional knockouts: Nex-Cre (excitatory neurons) vs. Dlx5/6-Cre (interneurons) to isolate cell-type-specific effects .
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Patient-derived iPSCs: Reprogram fibroblasts from X-linked hypertrichosis patients to study FGF13 haploinsufficiency in hair follicle organoids .
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Langendorff-perfused hearts: Assess APD prolongation in FGF13 knockdown murine atria .
Key validation step: Rescue experiments with AAV9-FGF13-VY in Fgf13<sup>−/y</sup> mice to confirm phenotype reversibility .
How do conflicting reports on FGF13’s role in cancer arise?
Data contradictions:
Resolution strategies:
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Perform isoform-specific siRNA knockdown in cancer vs. cardiac cell lines.
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Use ribosome profiling to quantify translational efficiency in FGF13<sup>−/−</sup> models .
What methodologies reliably detect FGF13 genetic variants?
Advanced sequencing pipelines:
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Whole-genome sequencing: Identify structural variants (e.g., chrXq27.1 insertions in hypertrichosis) .
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Long-read PacBio: Resolve repetitive regions near FGF13 locus to avoid false-negative CNV calls .
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Electrophysiological validation: Patch-clamp HEK293 cells expressing FGF13 missense mutants (e.g., R11C) to assess sodium channel kinetics .
Troubleshooting tip: Use MLPA (multiplex ligation-dependent probe amplification) to confirm copy number in ambiguous WGS results .
How does FGF13 interact with voltage-gated ion channels?
Mechanistic insights:
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Nav1.6 binding: FGF13-VY’s N-terminal domain (residues 1-78) stabilizes the channel’s inactivation gate, reducing persistent sodium current (I<sub>NaP</sub>) .
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Kv4.2 modulation: FGF13-S phosphorylates ERK1/2 to enhance A-type potassium currents in cardiomyocytes (I<sub>to</sub>) .
Experimental workflow:
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Co-immunoprecipitation with anti-Nav1.6 (NeuroMab 75-025).
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Voltage-clamp recordings in Xenopus oocytes co-expressing FGF13 and SCN8A .
What biomarkers indicate FGF13 dysregulation in clinical samples?
Validation protocol:
Product Science Overview
FGF13 is a protein-coding gene that plays a crucial role in various cellular processes. It shares 30-50% amino acid sequence identity with other FGFs and 60-70% identity with other members of the FGF11 subfamily . The primary structure of recombinant human FGF13 consists of a single polypeptide chain, which is biologically active and similar to its natural counterpart .
FGF13 is involved in the regulation of mitogenesis, differentiation, migration, angiogenesis, and wound healing . It activates signaling pathways such as the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) pathway, which is crucial for cell proliferation . Interestingly, FGF13’s mitogenic effects are mediated by FGFRs, despite its classification as an intracrine protein .
Recombinant human FGF13 is typically produced using an Escherichia coli expression system. This method allows for large-scale production of the protein, which can then be purified using column chromatography . The recombinant protein is often produced in two isoforms, rhFGF13A and rhFGF13B, both of which are soluble when expressed in E. coli .
Recombinant FGF13 has significant applications in biomedical research. It is used to study cell signaling interactions and pathways, particularly those involved in cell proliferation and differentiation . FGF13’s ability to promote the proliferation of NIH3T3 cells in the presence of heparin highlights its potential in therapeutic applications .
Mutations or dysregulation of FGF13 have been associated with various diseases, including developmental and epileptic encephalopathy and intellectual developmental disorders . Understanding the molecular mechanisms of FGF13 can provide insights into these conditions and potentially lead to the development of targeted therapies.
