glial cell line derived neurotrophic factor receptors


Summary: A family of GLYCOSYLPHOSPHATIDYLINOSITOL-anchored cell surface receptors that are specific for GLIAL CELL LINE-DERIVED NEUROTROPHIC FACTORS. They form a multi-component receptor complex with PROTO-ONCOGENE PROTEIN C-RET and regulate a variety of intracellular SIGNAL TRANSDUCTION PATHWAYS in conjunction with c-ret protein.

Top Publications

  1. Kim M, Kim H, Acharya S, Sohn H, Jun J, Chang I, et al. Ape1/Ref-1 induces glial cell-derived neurotropic factor (GDNF) responsiveness by upregulating GDNF receptor alpha1 expression. Mol Cell Biol. 2009;29:2264-77 pubmed publisher
  2. Parkash V, Goldman A. Comparison of GFL-GFRalpha complexes: further evidence relating GFL bend angle to RET signalling. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2009;65:551-8 pubmed publisher
    ..From sequence comparison, it is suggested that neuturin (the second GFL) adopts an artemin-like conformation, while persephin has a different conformation to the other three. ..
  3. Hobbs R, Seandel M, Falciatori I, Rafii S, Pandolfi P. Plzf regulates germline progenitor self-renewal by opposing mTORC1. Cell. 2010;142:468-79 pubmed publisher
  4. Iwashita T, Kruger G, Pardal R, Kiel M, Morrison S. Hirschsprung disease is linked to defects in neural crest stem cell function. Science. 2003;301:972-6 pubmed
    ..Gene expression profiling, combined with reverse genetics and analyses of stem cell function, suggests that Hirschsprung disease is caused by defects in neural crest stem cell function. ..
  5. Kokkinaki M, Lee T, He Z, Jiang J, Golestaneh N, Hofmann M, et al. The molecular signature of spermatogonial stem/progenitor cells in the 6-day-old mouse testis. Biol Reprod. 2009;80:707-17 pubmed publisher
    ..Collectively, this study provides novel molecular signatures for stem/progenitor spermatogonia and demonstrates a role for CSF1/CSF1R signaling in regulating their proliferation. ..
  6. Sidorova Y, Mätlik K, Paveliev M, Lindahl M, Piranen E, Milbrandt J, et al. Persephin signaling through GFRalpha1: the potential for the treatment of Parkinson's disease. Mol Cell Neurosci. 2010;44:223-32 pubmed publisher
    ..As the activation of GFRalpha1/RET was shown to rescue dopaminergic neurons, our results suggest the potential of persephin for the treatment of Parkinson's disease. ..
  7. Alladi P, Mahadevan A, Shankar S, Raju T, Muthane U. Expression of GDNF receptors GFRalpha1 and RET is preserved in substantia nigra pars compacta of aging Asian Indians. J Chem Neuroanat. 2010;40:43-52 pubmed publisher
    ..The latter possibility explains our earlier observation that the melanized nigral neurons are preserved with age in the Asian Indians. ..
  8. Garcia Lavandeira M, Diaz Rodriguez E, Garcia Rendueles M, Rodrigues J, Perez Romero S, Bravo S, et al. Functional role of the RET dependence receptor, GFRa co-receptors and ligands in the pituitary. Front Horm Res. 2010;38:127-38 pubmed publisher
    ..Recent data suggest that RET can also have a second role in pituitary plasticity through a second co-receptor GFRa2. ..
  9. Canty A, Dietze J, Harvey M, Enomoto H, Milbrandt J, Ibanez C. Regionalized loss of parvalbumin interneurons in the cerebral cortex of mice with deficits in GFRalpha1 signaling. J Neurosci. 2009;29:10695-705 pubmed publisher

More Information


  1. Gassei K, Ehmcke J, Dhir R, Schlatt S. Magnetic activated cell sorting allows isolation of spermatogonia from adult primate testes and reveals distinct GFRa1-positive subpopulations in men. J Med Primatol. 2010;39:83-91 pubmed publisher
    ..Magnetic activated cell sorting using anti-GFRalpha1 antibodies provides an enrichment strategy for spermatogonia from monkey and human testes. ..
  2. Choi Y, Tee J, Gallegos T, Shah M, Oishi H, Sakurai H, et al. Neuropeptide Y functions as a facilitator of GDNF-induced budding of the Wolffian duct. Development. 2009;136:4213-24 pubmed publisher
  3. Sada A, Suzuki A, Suzuki H, Saga Y. The RNA-binding protein NANOS2 is required to maintain murine spermatogonial stem cells. Science. 2009;325:1394-8 pubmed publisher
    ..Thus, NANOS2 is a key stem cell regulator that is expressed in self-renewing spermatogonial stem cells and maintains the stem cell state during murine spermatogenesis. ..
  4. Shneider N, Brown M, Smith C, Pickel J, Alvarez F. Gamma motor neurons express distinct genetic markers at birth and require muscle spindle-derived GDNF for postnatal survival. Neural Dev. 2009;4:42 pubmed publisher
    ..This provides a mouse model with which to explore the specific role of gamma-fusimotor activity in motor behaviors. ..
  5. Gonzalez Aparicio R, Flores J, Fernandez Espejo E. Antiparkinsonian trophic action of glial cell line-derived neurotrophic factor and transforming growth factor ?1 is enhanced after co-infusion in rats. Exp Neurol. 2010;226:136-47 pubmed publisher
    ..Functional recovery and improvement of TH signal in the nigrostriatal system were long-lasting and sustained, remaining after cessation of trophic infusion...
  6. Yoong L, Wan G, Too H. GDNF-induced cell signaling and neurite outgrowths are differentially mediated by GFRalpha1 isoforms. Mol Cell Neurosci. 2009;41:464-73 pubmed publisher
    ..This study demonstrates the hitherto unrecognized roles of GFRalpha1 isoforms in the activation of distinct signaling pathways and in neurite outgrowths. ..
  7. Bourane S, Garces A, Venteo S, Pattyn A, Hubert T, Fichard A, et al. Low-threshold mechanoreceptor subtypes selectively express MafA and are specified by Ret signaling. Neuron. 2009;64:857-70 pubmed publisher
    ..Our results provide evidence that genetic interactions involving Ret and MafA progressively promote the differentiation and diversification of LTMs. ..
  8. Kokkinaki M, Lee T, He Z, Jiang J, Golestaneh N, Hofmann M, et al. Age affects gene expression in mouse spermatogonial stem/progenitor cells. Reproduction. 2010;139:1011-20 pubmed publisher
    ..On the other hand, the expression levels of the genes encoding the SSC markers Gfra1 and Plzf did not seem to be significantly altered by age, indicating that age affects only certain SSC/progenitor properties. ..
  9. Keast J, Forrest S, Osborne P. Sciatic nerve injury in adult rats causes distinct changes in the central projections of sensory neurons expressing different glial cell line-derived neurotrophic factor family receptors. J Comp Neurol. 2010;518:3024-45 pubmed publisher
    ..Our results suggest that the DRG neuronal populations targeted by GDNF, neurturin, or artemin and the effect of exogenous GFLs could change significantly after a peripheral nerve injury. ..
  10. Narita N, Tanemura A, Murali R, Scolyer R, Huang S, Arigami T, et al. Functional RET G691S polymorphism in cutaneous malignant melanoma. Oncogene. 2009;28:3058-68 pubmed publisher
    ..The study demonstrates that RETp is frequently found in cutaneous melanoma, particularly desmoplastic subtypes, and responds to GDNF inducing events favorable for tumor progression. ..
  11. Ledda F. Ligand-induced cell adhesion as a new mechanism to promote synapse formation. Cell Adh Migr. 2007;1:137-9 pubmed
    ..In this overview, I summarize the current concepts of synapse formation in the limelight of this new mechanism of ligand-induced cell adhesion. ..
  12. Calender A. [Multiple endocrine neoplasia: genetic aspects]. Bull Acad Natl Med. 2010;194:81-95; discussion 95-6 pubmed
  13. Pruett B, Salvatore M. GFR ?-1 receptor expression in the aging nigrostriatal and mesoaccumbens pathways. J Neurochem. 2010;115:707-15 pubmed publisher
  14. Gomes C, Simões P, Canas P, Quiroz C, Sebastião A, Ferré S, et al. GDNF control of the glutamatergic cortico-striatal pathway requires tonic activation of adenosine A receptors. J Neurochem. 2009;108:1208-19 pubmed publisher
    ..The results provide the first functional and morphological evidence that GDNF controls cortico-striatal glutamatergic pathways in a manner largely dependent on the co-activation of adenosine A(2A) receptors. ..
  15. Souza R, Romano Silva M, Lieberman J, Meltzer H, MacNeil L, Culotti J, et al. Genetic association of the GDNF alpha-receptor genes with schizophrenia and clozapine response. J Psychiatr Res. 2010;44:700-6 pubmed publisher
    ..We also found nominally-significant evidence for interactions between GFRA1, 2 and 3 associated with schizophrenia and clozapine response, consistent with the locations of these three genes within linkage regions for schizophrenia. ..
  16. Kanter Schlifke I, Fjord Larsen L, Kusk P, Angehagen M, Wahlberg L, Kokaia M. GDNF released from encapsulated cells suppresses seizure activity in the epileptic hippocampus. Exp Neurol. 2009;216:413-9 pubmed publisher
    ..We demonstrate here that encapsulated cells, which are genetically modified to produce and release GDNF, can suppress recurrent generalized seizures when implanted into the hippocampus of kindled rats. ..
  17. Nakagawa T, Sharma M, Nabeshima Y, Braun R, Yoshida S. Functional hierarchy and reversibility within the murine spermatogenic stem cell compartment. Science. 2010;328:62-7 pubmed publisher
    ..Thus, there are multiple and reversible paths from stem cells to differentiation, and these may also occur in other systems. ..
  18. Plaza Menacho I, Morandi A, Robertson D, Pancholi S, Drury S, Dowsett M, et al. Targeting the receptor tyrosine kinase RET sensitizes breast cancer cells to tamoxifen treatment and reveals a role for RET in endocrine resistance. Oncogene. 2010;29:4648-57 pubmed publisher
    ..Together these findings identify RET as a potentially important therapeutic target in ERalpha-positive breast cancers and in particular in tamoxifen-resistant tumors. ..
  19. Qiao S, Iwashita T, Ichihara M, Murakumo Y, Yamaguchi A, Isogai M, et al. Increased expression of glial cell line-derived neurotrophic factor and neurturin in a case of colon adenocarcinoma associated with diffuse ganglioneuromatosis. Clin Neuropathol. 2009;28:105-12 pubmed
    ..These findings suggested that GDNF and NTN expression in adenocarcinoma cells may play an important role in the pathogenesis of GN. ..
  20. Lücking C, Lichtner P, Kramer E, Gieger C, Illig T, Dichgans M, et al. Polymorphisms in the receptor for GDNF (RET) are not associated with Parkinson's disease in Southern Germany. Neurobiol Aging. 2010;31:167-8 pubmed publisher
  21. Zhu D, Luo D, Luo G, Wang B, Gao J. [Artemin and GFRalpha3 expressions and their relevance to perineural invasiveness and metastasis of pancreatic carcinoma]. Nan Fang Yi Ke Da Xue Xue Bao. 2009;29:428-32 pubmed
    ..512-/+0.017, P<0.05). Artemin and GFRalpha3 expressions may play an important role in perineural invasion of pancreatic carcinoma and can be used a useful indicators for evaluating the biological behavior of pancreatic carcinomas. ..
  22. Carnicella S, Ahmadiantehrani S, Janak P, Ron D. GDNF is an endogenous negative regulator of ethanol-mediated reward and of ethanol consumption after a period of abstinence. Alcohol Clin Exp Res. 2009;33:1012-24 pubmed publisher
    ..Our results suggest that endogenous GDNF negatively regulates the rewarding effect of ethanol and ethanol-drinking behaviors after a period of abstinence. ..
  23. Spinnler K, Kohn F, Schwarzer U, Mayerhofer A. Glial cell line-derived neurotrophic factor is constitutively produced by human testicular peritubular cells and may contribute to the spermatogonial stem cell niche in man. Hum Reprod. 2010;25:2181-7 pubmed publisher
    ..TNF-alpha and tryptase had no effect on the secretion of GDNF by HTPCs or HTPC-Fs. Peritubular cells in testes of normal and sub-/infertile men produce GDNF and are likely constitutive contributors of the SSC niche in the human testis. ..
  24. Facello B, Castaldo L, De Martino L, Lucini C. Glial cell line-derived neurotrophic factor in Purkinje cells of adult zebrafish: an autocrine mode of action?. Neurosci Lett. 2009;465:133-7 pubmed publisher
    ..These results demonstrated the expression of the GDNF receptorial complex in adult zebrafish cerebellum and suggest an autocrine mode of action of GDNF in Purkinje cells. ..
  25. Grozdanic S, Lazic T, Kuehn M, Harper M, Kardon R, Kwon Y, et al. Exogenous modulation of intrinsic optic nerve neuroprotective activity. Graefes Arch Clin Exp Ophthalmol. 2010;248:1105-16 pubmed publisher
    ..001 respectively) compared to non-treated animals. Continuous release of neurotrophic growth factors (NGFs) significantly protects optic nerve function in the experimental model of retinal ischemia observed by PLR analysis. ..
  26. Li J, Klein C, Liang C, Rauch R, Kawamura K, Hsueh A. Autocrine regulation of early embryonic development by the artemin-GFRA3 (GDNF family receptor-alpha 3) signaling system in mice. FEBS Lett. 2009;583:2479-85 pubmed publisher
    ..The genome-wide survey of ligand-receptor pairs and early embryo cultures provided a better understanding of autocrine/paracrine embryonic factors important for optimal blastocyst development. ..
  27. Piirsoo M, Kaljas A, Tamm K, Timmusk T. Expression of NGF and GDNF family members and their receptors during peripheral nerve development and differentiation of Schwann cells in vitro. Neurosci Lett. 2010;469:135-40 pubmed publisher
    ..Our results demonstrate specific expression patterns of NGF and GDNF family ligands and their receptors during differentiation of Schwann cells in vivo and in vitro. ..
  28. Gassei K, Ehmcke J, Schlatt S. Efficient enrichment of undifferentiated GFR alpha 1+ spermatogonia from immature rat testis by magnetic activated cell sorting. Cell Tissue Res. 2009;337:177-83 pubmed publisher
    ..We conclude that GFRalpha1 serves as a suitable surface marker for the enrichment of rat spermatogonia, and that the large-volume Midi-MACS separation system is superior to the routinely used small-volume Mini-MACS separation system. ..
  29. Garcia N, Santafe M, Tomas M, Lanuza M, Besalduch N, Priego M, et al. The glial cell line-derived neurotrophic factor (GDNF) does not acutely change acetylcholine release in developing and adult neuromuscular junction. Neurosci Lett. 2010;480:127-31 pubmed publisher
    ..Our findings indicate that GDNF (unlike neurotrophins) does not acutely modulate transmitter release during the developmental process of synapse elimination nor as the NMJ matures. ..
  30. Wan G, Too H. A specific isoform of glial cell line-derived neurotrophic factor family receptor alpha 1 regulates RhoA expression and glioma cell migration. J Neurochem. 2010;115:759-70 pubmed publisher
    ..Taken together, these unanticipated results indicate that GFR?1b is involved in glioma migration through glial cell line-derived neurotrophic factor -GFR?1b-NCAM signaling complex and modulation of RhoA expression. ..
  31. Gil Z, Cavel O, Kelly K, Brader P, Rein A, Gao S, et al. Paracrine regulation of pancreatic cancer cell invasion by peripheral nerves. J Natl Cancer Inst. 2010;102:107-18 pubmed publisher
    ..These data provide evidence for paracrine regulation of pancreatic cancer invasion by nerves, which may have important implications for potential therapy directed against nerve invasion by cancer. ..
  32. Farhi J, Ao A, Fisch B, Zhang X, Garor R, Abir R. Glial cell line-derived neurotrophic factor (GDNF) and its receptors in human ovaries from fetuses, girls, and women. Fertil Steril. 2010;93:2565-71 pubmed publisher
    ..The presence of the receptors of GDNF in the GCs of human primordial follicles suggests that GDNF may be involved in the regulation of primordial follicular activation. ..
  33. Grisanti L, Falciatori I, Grasso M, Dovere L, Fera S, Muciaccia B, et al. Identification of spermatogonial stem cell subsets by morphological analysis and prospective isolation. Stem Cells. 2009;27:3043-52 pubmed publisher
    ..Our data support the hypothesis of the existence of SSC subsets and reveal a previously unrecognized heterogeneity in the expression profile of As spermatogonia in vivo. ..
  34. Wang S, Albers K. Behavioral and cellular level changes in the aging somatosensory system. Ann N Y Acad Sci. 2009;1170:745-9 pubmed publisher
    ..The lack of change in aged neurons suggests that differences in TRPV1 responses occur with aging in the somatosensory system. ..
  35. Madduri S, Papaloïzos M, Gander B. Synergistic effect of GDNF and NGF on axonal branching and elongation in vitro. Neurosci Res. 2009;65:88-97 pubmed publisher
    ..This information should be relevant for the development of implants containing NTFs and on drug therapy of damaged peripheral nerves. ..
  36. Lavedan C, Licamele L, Volpi S, Hamilton J, Heaton C, Mack K, et al. Association of the NPAS3 gene and five other loci with response to the antipsychotic iloperidone identified in a whole genome association study. Mol Psychiatry. 2009;14:804-19 pubmed publisher
    ..These results provide new insight into response to iloperidone, developed with the ultimate goal of directing therapy to patients with the highest benefit-to-risk ratio. ..
  37. Ibanez C. Beyond the cell surface: new mechanisms of receptor function. Biochem Biophys Res Commun. 2010;396:24-7 pubmed publisher
    ..This plethora of unconventional mechanisms is likely to be a feature common to several other receptors and considerably expands our view of cell surface receptor function. ..
  38. Tyagi G, Carnes K, Morrow C, Kostereva N, Ekman G, Meling D, et al. Loss of Etv5 decreases proliferation and RET levels in neonatal mouse testicular germ cells and causes an abnormal first wave of spermatogenesis. Biol Reprod. 2009;81:258-66 pubmed publisher
    ..In addition, ETV5 has critical effects on neonatal spermatogonial proliferation, which may involve impaired signaling through the RET receptor. ..