GFRA3 explained

GDNF family receptor alpha-3 (GFRα3), also known as the artemin receptor, is a protein that in humans is encoded by the GFRA3 gene.^{[1] [2]}

Function

The protein encoded by this gene is a glycosylphosphatidylinositol(GPI)-linked cell surface receptor and a member of the GDNF receptor family. It forms a signaling receptor complex with RET tyrosine kinase receptor and binds the artemin ligand.

In mouse models of osteoarthritis, GFRα3 was upregulated in sensory nerves. Treating arthritic mice with monoclonal antibodies that bind to GFRα3 prevents artemin from binding there and signaling pain. Treated mice were able to use their limbs again two hours post-treatment.^[3]

See also

• GFRα

Further reading

• Wang X, Baloh RH, Milbrandt J, Garcia KC . Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors . Structure . 14 . 6 . 1083–92 . Jun 2006 . 16765900 . 10.1016/j.str.2006.05.010 . free .
• Zhang Z, Henzel WJ . Signal peptide prediction based on analysis of experimentally verified cleavage sites . Protein Science . 13 . 10 . 2819–24 . October 2004 . 15340161 . 2286551 . 10.1110/ps.04682504 .
• Gimm O, Dziema H, Brown J, Hoang-Vu C, Hinze R, Dralle H, Mulligan LM, Eng C . Over-representation of a germline variant in the gene encoding RET co-receptor GFRalpha-1 but not GFRalpha-2 or GFRalpha-3 in cases with sporadic medullary thyroid carcinoma . Oncogene . 20 . 17 . 2161–70 . Apr 2001 . 11360200 . 10.1038/sj.onc.1204289 . free .
• Onochie CI, Korngut LM, Vanhorne JB, Myers SM, Michaud D, Mulligan LM . Characterisation of the human GFRalpha-3 locus and investigation of the gene in Hirschsprung disease . Journal of Medical Genetics . 37 . 9 . 674–9 . Sep 2000 . 10978357 . 1734691 . 10.1136/jmg.37.9.674 .
• Baloh RH, Tansey MG, Lampe PA, Fahrner TJ, Enomoto H, Simburger KS, Leitner ML, Araki T, Johnson EM, Milbrandt J . Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex . Neuron . 21 . 6 . 1291–302 . December 1998 . 9883723 . 10.1016/S0896-6273(00)80649-2 . 18633359 . free .
• Baloh RH, Gorodinsky A, Golden JP, Tansey MG, Keck CL, Popescu NC, Johnson EM, Milbrandt J . GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor family . Proceedings of the National Academy of Sciences of the United States of America . 95 . 10 . 5801–6 . May 1998 . 9576965 . 20460 . 10.1073/pnas.95.10.5801 . 1998PNAS...95.5801B . free .
• Masure S, Cik M, Pangalos MN, Bonaventure P, Verhasselt P, Lesage AS, Leysen JE, Gordon RD . Molecular cloning, expression and tissue distribution of glial-cell-line-derived neurotrophic factor family receptor alpha-3 (GFRalpha-3) . European Journal of Biochemistry . 251 . 3 . 622–30 . Feb 1998 . 9490034 . 10.1046/j.1432-1327.1998.2510622.x . free .
• Robertson NG, Khetarpal U, Gutiérrez-Espeleta GA, Bieber FR, Morton CC . Isolation of novel and known genes from a human fetal cochlear cDNA library using subtractive hybridization and differential screening . Genomics . 23 . 1 . 42–50 . September 1994 . 7829101 . 10.1006/geno.1994.1457 .

Notes and References

1. Jing S, Yu Y, Fang M, Hu Z, Holst PL, Boone T, Delaney J, Schultz H, Zhou R, Fox GM . GFRalpha-2 and GFRalpha-3 are two new receptors for ligands of the GDNF family . The Journal of Biological Chemistry . 272 . 52 . 33111–7 . Dec 1997 . 9407096 . 10.1074/jbc.272.52.33111 . free .
2. Web site: Entrez Gene: GFRA3 GDNF family receptor alpha 3.
3. Web site: Irving. Michael. 2022-01-31. "Pain pathway" a promising new drug target to treat osteoarthritis pain. 2022-02-01. New Atlas. en-US.