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Gene Review

Gfra1  -  GDNF family receptor alpha 1

Rattus norvegicus

Synonyms: GDNF family receptor alpha-1, GDNF receptor alpha-1, GDNFR-alpha-1, GFR-alpha-1, Gdnfra, ...
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Disease relevance of Gfra1

  • In addition, this study demonstrates expression of GDNF family receptor-alpha 3 (GFR alpha 3) mRNA in most adrenergic, but only in a minor part (5.3%) of the penis-projecting adult rat major pelvic ganglion neurons, as well as in almost half (45.6%) of the penile S1 dorsal root ganglion neurons [1].
  • These data indicate that the gain-of-function MEN2B mutation does not abrogate ligand responsiveness of Ret and suggest that the presence of Ret ligand could play a role in the pathogenesis of the MEN2B syndrome [2].

High impact information on Gfra1


Biological context of Gfra1


Anatomical context of Gfra1


Associations of Gfra1 with chemical compounds

  • They exert their biological effects by activating the RET tyrosine kinase in the presence of a GPI-linked coreceptor, either GFR alpha 1 (considered to be the favored coreceptor for GDNF) or GFR alpha 2 (the preferred NTN coreceptor) [12].
  • GFR alpha-1/GAD co-expression was found mainly in the stratum (s) pyramidale (29-37%) and s. oriens (20-25%) [14].
  • In addition, acute or chronic lithium treatments did not change the levels of Trk B, RET, or GDNFR-alpha immunoreactivity [15].

Regulatory relationships of Gfra1


Other interactions of Gfra1

  • Thus, spinal motoneurons are highly heterogeneous in their expression of receptors for neurotrophic factors of the GDNF family, but their differing responses to NTN are not correlated with expression levels of Gfra1 or Gfra2 [12].
  • Responsiveness to neurturin of subpopulations of embryonic rat spinal motoneuron does not correlate with expression of GFR alpha 1 or GFR alpha 2 [12].
  • Although GDNF, NTN and Ret mRNA levels were at the limit of detection, RNase protection assays revealed relatively high amounts of GFR alpha-1 and GFR alpha transcripts [16].

Analytical, diagnostic and therapeutic context of Gfra1


  1. Glial cell line-derived neurotrophic factor is expressed in penis of adult rat and retrogradely transported in penile parasympathetic and sensory nerves. Laurikainen, A., Hiltunen, J.O., Vanhatalo, S., Klinge, E., Saarma, M. Cell Tissue Res. (2000) [Pubmed]
  2. Ligand stimulation of a Ret chimeric receptor carrying the activating mutation responsible for the multiple endocrine neoplasia type 2B. Rizzo, C., Califano, D., Colucci-D'Amato, G.L., De Vita, G., D'Alessio, A., Dathan, N.A., Fusco, A., Monaco, C., Santelli, G., Vecchio, G., Santoro, M., de Franciscis, V. J. Biol. Chem. (1996) [Pubmed]
  3. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Jing, S., Wen, D., Yu, Y., Holst, P.L., Luo, Y., Fang, M., Tamir, R., Antonio, L., Hu, Z., Cupples, R., Louis, J.C., Hu, S., Altrock, B.W., Fox, G.M. Cell (1996) [Pubmed]
  4. Conservation of spermatogonial stem cell self-renewal signaling between mouse and rat. Ryu, B.Y., Kubota, H., Avarbock, M.R., Brinster, R.L. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  5. Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha. Suvanto, P., Wartiovaara, K., Lindahl, M., Arumae, U., Moshnyakov, M., Horelli-Kuitunen, N., Airaksinen, M.S., Palotie, A., Sariola, H., Saarma, M. Hum. Mol. Genet. (1997) [Pubmed]
  6. Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptor-alpha indicates multiple mechanisms of trophic actions in the adult rat CNS. Trupp, M., Belluardo, N., Funakoshi, H., Ibáñez, C.F. J. Neurosci. (1997) [Pubmed]
  7. Retrograde propagation of GDNF-mediated signals in sympathetic neurons. Coulpier, M., Ibáñez, C.F. Mol. Cell. Neurosci. (2004) [Pubmed]
  8. Differential in vivo effects of neurturin and glial cell-line-derived neurotrophic factor. Hoane, M.R., Gulwadi, A.G., Morrison, S., Hovanesian, G., Lindner, M.D., Tao, W. Exp. Neurol. (1999) [Pubmed]
  9. Localization of glial cell line-derived neurotrophic factor receptor alpha and c-ret mRNA in rat central nervous system. Glazner, G.W., Mu, X., Springer, J.E. J. Comp. Neurol. (1998) [Pubmed]
  10. Glial cell line-derived neurotrophic factor and nerve growth factor receptor mRNAs are expressed in distinct subgroups of dorsal root ganglion neurons and are differentially regulated by peripheral axotomy in the rat. Kashiba, H., Hyon, B., Senba, E. Neurosci. Lett. (1998) [Pubmed]
  11. Up-regulation of GDNFR-alpha and c-ret mRNA in facial motor neurons following facial nerve injury in the rat. Burazin, T.C., Gundlach, A.L. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  12. Responsiveness to neurturin of subpopulations of embryonic rat spinal motoneuron does not correlate with expression of GFR alpha 1 or GFR alpha 2. Garcès, A., Livet, J., Grillet, N., Henderson, C.E., Delapeyrière, O. Dev. Dyn. (2001) [Pubmed]
  13. Expression of GFR alpha-1, GFR alpha-2, and c-Ret mRNAs in rat adrenal gland. Schober, A., Arumäe, U., Saarma, M., Unsicker, K. J. Neurocytol. (2000) [Pubmed]
  14. GFR alpha-1 is expressed in parvalbumin GABAergic neurons in the hippocampus. Sarabi, A., Hoffer, B.J., Olson, L., Morales, M. Brain Res. (2000) [Pubmed]
  15. Chronic lithium treatment increases the expression of brain-derived neurotrophic factor in the rat brain. Fukumoto, T., Morinobu, S., Okamoto, Y., Kagaya, A., Yamawaki, S. Psychopharmacology (Berl.) (2001) [Pubmed]
  16. Differential regulation of GDNF, neurturin, and their receptors in primary cultures of rat glial cells. Rémy, S., Naveilhan, P., Brachet, P., Neveu, I. J. Neurosci. Res. (2001) [Pubmed]
  17. Glial cell line-derived neurotrophic factor protects dopaminergic neurons from 6-hydroxydopamine toxicity in vitro. Eggert, K., Schlegel, J., Oertel, W., Würz, C., Krieg, J.C., Vedder, H. Neurosci. Lett. (1999) [Pubmed]
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