Background and Biological Significance of GFRA2

GDNF Family Receptor Alpha 2 (GFRA2, also known as GFRα2 or RETL2) is a glycosylphosphatidylinositol (GPI)-anchored cell-surface co-receptor and a member of the GFRα family of proteins. It serves as the preferred high-affinity binding partner for neurturin (NRTN), a member of the glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs).

Upon binding neurturin, GFRA2 recruits and activates the transmembrane receptor tyrosine kinase RET, initiating downstream signaling cascades including the MAPK, PI3K/AKT, and PLC-γ pathways. These signals regulate neuronal survival, differentiation, axonal growth, and synaptic plasticity, particularly in parasympathetic, enteric, and sensory neurons.

GFRA2 is expressed in multiple tissues during development and in the adult organism, including the nervous system and various peripheral organs. Research into GFRA2 biology has implications for understanding neurodegenerative conditions, enteric nervous system development, and pain perception pathways.

Product Handling and Storage Recommendations

To maintain the biological activity and structural integrity of Recombinant Human GFRA2 Protein, adherence to proper handling and storage protocols is essential. The following general best-practice guidelines apply to recombinant proteins of this class:

• Upon receipt: Inspect the product and centrifuge briefly if liquid condensation is observed on the vial cap or sides before opening.
• Reconstitution: If supplied in lyophilized form, reconstitute using sterile phosphate-buffered saline (PBS) or the buffer specified in the product datasheet. Allow the vial to equilibrate to room temperature before reconstitution to minimize aggregation.
• Storage temperature: Store at −20 °C or −80 °C for long-term stability. Avoid repeated freeze-thaw cycles, which can reduce activity and promote aggregation.
• Aliquoting: Prepare single-use aliquots immediately after reconstitution to avoid repeated freeze-thaw cycles.
• Working solutions: Dilute to the required working concentration in a carrier protein-containing buffer (e.g., 0.1% BSA in PBS) to stabilize the protein during experiments.

Note: Always refer to the specific product datasheet supplied with SKU rp365087 for lot-specific storage conditions, concentration, and expiry information.

Recommended Research Applications

Recombinant Human GFRA2 Protein is suitable for a range of in vitro and cell-based research applications. Representative uses include:

• Ligand-binding assays: Characterize the binding affinity and kinetics of GFRA2 interactions with neurturin or other GFL family members using surface plasmon resonance (SPR), ELISA-based binding assays, or bead-based multiplex platforms.
• Cell signaling studies: Use soluble recombinant GFRA2 to study RET transactivation, downstream MAPK and AKT phosphorylation, and neuronal survival in cell culture models.
• Functional blocking and neutralization: Employ the protein as a competitive inhibitor or decoy receptor to dissect GFRA2-mediated signaling from other co-receptor pathways.
• Protein-protein interaction studies: Identify novel GFRA2-interacting proteins using pull-down assays, co-immunoprecipitation, or proximity ligation approaches.
• ELISA and Western blot standards: Serve as a positive control or standard curve reference in immunoassays detecting endogenous GFRA2.
• Drug discovery screening: Incorporate into high-throughput assay formats to screen small molecule libraries for modulators of the GFRA2–neurturin–RET signaling axis.

Quality, Purity, and Regulatory Considerations

Recombinant Human GFRA2 Protein (rp365087) from Aladdin Scientific is manufactured to research-grade standards. Key quality considerations include:

• Purity: Recombinant proteins in this class are typically verified by SDS-PAGE and/or HPLC analysis. Refer to the Certificate of Analysis (CoA) provided with each lot for confirmed purity data.
• Endotoxin testing: Endotoxin levels should be assessed and minimized for cell-based assays. Consult the lot-specific CoA for endotoxin values.
• Biological activity: Functional activity may be verified using cell-based bioassays measuring RET phosphorylation or neurite outgrowth in responsive cell lines. Refer to the datasheet for activity specifications.
• Regulatory status: This product is supplied for research use only (RUO) and is not intended for human or veterinary diagnostic or therapeutic applications. It has not been evaluated by regulatory agencies for clinical use.
• Lot-to-lot consistency: Contact Aladdin Scientific customer support for multi-lot qualification data if consistency across experiments is a critical requirement.