Affinage

GFRA1

GDNF family receptor alpha-1 · UniProt P56159

Length
465 aa
Mass
51.5 kDa
Annotated
2026-04-28
69 papers in source corpus 21 papers cited in narrative 21 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GFRA1 is a GPI-anchored cell-surface co-receptor that orchestrates GDNF-dependent signaling through the RET receptor tyrosine kinase and, independently of RET, through lysosomal and SRC-dependent pathways that regulate autophagy and cell survival. GFRA1 binds GDNF with high selectivity, forming a ternary complex with RET that triggers RET autophosphorylation and downstream PI3K/AKT and ERK activation; this complex requires the first three cadherin-like domains of RET and is modulated by O-linked sialylation of GFRA1 by ST3GAL1 (PMID:8674117, PMID:14514671, PMID:30040982). In a RET-independent mode, GFRA1 interacts with the lysosomal calcium channel MCOLN1 to activate Ca²⁺-dependent TFEB-driven autophagy, a mechanism exploited in tumor dormancy and chemoresistance in osteosarcoma, gastrointestinal stromal tumors, and glioblastoma (PMID:35288241, PMID:27754745, PMID:39085346). Biallelic loss-of-function variants in GFRA1 cause autosomal recessive bilateral renal agenesis in humans, and hypomorphic Gfra1 mice develop Hirschsprung disease, reflecting essential roles in ureteric bud outgrowth and enteric nervous system colonization (PMID:33020172, PMID:30594740).

Mechanistic history

Synthesis pass · year-by-year structured walk · 12 steps
  1. 1996 High

    The founding question—how GDNF signals through RET—was resolved by identifying GFRA1 as a GPI-linked accessory receptor that binds GDNF and presents it to RET, thereby reconstituting a stepwise GDNF→GFRA1→RET signaling complex.

    Evidence Expression cloning, ligand-binding assays, RET autophosphorylation, soluble receptor reconstitution, and RET-Fc blockade in cell lines

    PMID:8674117

    Open questions at the time
    • Stoichiometry of the ternary complex not defined
    • Structural basis for GDNF–GFRA1 interface unknown at this point
    • Whether GFRA1 signals independently of RET not addressed
  2. 2000 Medium

    It was unknown whether GFRA1 expression is constitutive or regulated; depolarization-driven Ca²⁺ influx through L-type channels was shown to upregulate GFRA1 mRNA in peripheral neurons, shifting neurotrophic factor responsiveness from neurturin to GDNF.

    Evidence Competitive RT-PCR in cultured embryonic sympathetic, parasympathetic, and sensory neurons under KCl depolarization with L-type Ca²⁺ channel antagonists

    PMID:10704393

    Open questions at the time
    • Transcription factor mediating activity-dependent GFRA1 induction not identified
    • In vivo relevance of activity-dependent switch not tested
  3. 2001 Medium

    Whether GFRA1 has RET-independent functions in vivo was tested by genetic epistasis: constitutively active RET(Men2B) failed to rescue intestinal aganglionosis in Gfra1-null mice, establishing that GFRA1 is essential for enteric progenitor colonization upstream of or parallel to RET activation.

    Evidence RET(Men2B) transgene crossed into Gfra1-null mouse background, histopathological analysis

    PMID:11779046

    Open questions at the time
    • The RET-independent function of GFRA1 in enteric development molecularly undefined
    • Whether GFRA1 is required cell-autonomously in enteric neural crest not resolved
  4. 2003 High

    The molecular interface between the ternary complex and RET was mapped: the first three cadherin-like domains of RET form the GDNF–GFRA1 binding surface, and GFRA1 undergoes rapid ligand-dependent endocytosis even without RET, revealing a RET-independent trafficking route.

    Evidence Homologue-scanning mutagenesis of RET ectodomain chimeras (binding assays); internalization kinetics in RET-negative neuroblastoma and fibroblast lines

    PMID:12701883 PMID:14514671

    Open questions at the time
    • Atomic-resolution structure of the ternary complex not yet available
    • Cargo and destination of internalized GFRA1 in RET-negative cells unknown
  5. 2005 High

    The ligand specificity of GFRA1 was quantified: GFRA1 is >10,000-fold more selective for GDNF over artemin, and an anti-GFRA1 antibody blocks GDNF- but not artemin-mediated neuron survival, resolving prior ambiguity about cross-reactivity among GFR-alpha family members.

    Evidence Cell-free binding, competitive radioligand binding, ERK/AKT and RET phosphorylation dose-response, antibody neutralization in DRG neurons

    PMID:15709767

    Open questions at the time
    • Structural basis for ligand discrimination not determined
    • Whether very high local artemin concentrations could engage GFRA1 in vivo not excluded
  6. 2007 High

    GFRA1 was shown to function beyond the nervous system: in spermatogonial stem cells, GFRA1 knockdown abolished RET phosphorylation and drove differentiation, and in breast cancer cells, paracrine GDNF–GFRA1–RET signaling promoted proliferation and scattering.

    Evidence siRNA knockdown in mouse type A spermatogonia with colony-forming/differentiation assays; GDNF stimulation of MCF7 breast cancer cells and xenograft paracrine analysis

    PMID:17625109 PMID:18089803

    Open questions at the time
    • Whether GFRA1 marks a functionally homogeneous SSC population unclear
    • Downstream RET-dependent transcriptional program in SSCs not mapped
  7. 2010 Medium

    Epigenetic control of GFRA1 transcription was demonstrated: histone H3 methylation and acetylation at the Gfra1 promoter regulate its expression in germ cells, and an antisense lncRNA (lncRNA033862) interacts with Gfra1 chromatin to sustain expression required for SSC survival.

    Evidence ChIP-qPCR with HDAC/KDM1 inhibitors in GC-1 cells; lncRNA profiling and knockdown with SSC transplantation assay

    PMID:20856864 PMID:26962690

    Open questions at the time
    • Which specific histone marks are necessary versus sufficient not dissected
    • Direct versus indirect lncRNA mechanism not resolved
    • Whether epigenetic regulation is conserved in human SSCs untested
  8. 2016 High

    A RET-independent signaling axis was molecularly defined: in osteosarcoma, GFRA1 activates SRC and AMPK-dependent autophagy to confer cisplatin resistance, with NFKB1-mediated GFRA1 upregulation creating a feed-forward loop.

    Evidence GFRA1 overexpression/knockdown, SRC and AMPK phosphorylation assays, autophagy flux, xenograft models

    PMID:27754745

    Open questions at the time
    • Direct physical interaction partner mediating RET-independent SRC activation not identified
    • Whether the SRC-AMPK autophagy axis operates in non-cancer cells unknown
  9. 2018 Medium

    Post-translational regulation of GFRA1 function was uncovered: ST3GAL1-mediated O-linked sialylation of GFRA1 is required for GDNF-induced RET, AKT, and ERα phosphorylation in breast cancer cells, and Gfra1 hypomorphic mice develop Hirschsprung disease with goblet cell dysplasia as a primary pathogenic mechanism.

    Evidence ST3GAL1 silencing with phosphorylation readouts in breast cancer cells; Gfra1 hypomorphic mouse model with histopathological disease progression analysis

    PMID:30040982 PMID:30594740

    Open questions at the time
    • Specific sialylation sites on GFRA1 not mapped
    • Whether goblet cell defect is cell-autonomous or secondary to enteric neuron loss not resolved
  10. 2020 Medium

    Human disease causality was established: biallelic loss-of-function GFRA1 variants cause autosomal recessive bilateral renal agenesis, and small-molecule RET agonists revealed that GFRA1 co-expression biases RET downstream signaling between AKT and ERK pathways.

    Evidence Exome/genome sequencing in consanguineous families with Sanger confirmation; structure-activity studies of Q compounds in cells ± GFRA1

    PMID:32245892 PMID:33020172

    Open questions at the time
    • No functional rescue of human variants performed
    • Mechanism by which GFRA1 biases RET signaling toward specific pathways structurally unexplained
  11. 2022 Medium

    The molecular basis of GFRA1's RET-independent autophagy role was identified: GFRA1 physically interacts with the lysosomal Ca²⁺ channel MCOLN1, activating Ca²⁺-dependent TFEB signaling to upregulate lysosome biogenesis and autophagy flux, promoting tumor dormancy and drug resistance.

    Evidence Co-immunoprecipitation of GFRA1 and MCOLN1, TFEB reporter assays, calcium signaling, loss/gain-of-function in GIST cells in vitro and in vivo

    PMID:35288241

    Open questions at the time
    • Whether GFRA1–MCOLN1 interaction is direct or in a complex not established
    • GFRA1 domain required for MCOLN1 interaction not mapped
    • Relevance of this pathway in normal physiology unknown
  12. 2024 Medium

    Upstream regulators of GFRA1 expression were extended: ASH2L-dependent H3K4me3 controls Gfra1 transcription in the ureteric bud lineage, PTN/SDC2 signaling from Leydig cells maintains GFRA1 in human spermatogonia, and GFRA1 knockout sensitized patient-derived glioblastoma spheroids to chemo- and radiotherapy.

    Evidence Conditional Ash2l KO with CUT&Tag in mouse UB; SDC2 knockdown/PTN rescue in human SSC lines; CRISPR KO of GFRA1 in patient-derived GBM spheroids with drug/radiation survival assays

    PMID:36758123 PMID:39085346 PMID:39285301

    Open questions at the time
    • Whether ASH2L directly binds Gfra1 promoter or acts indirectly not shown
    • Whether PTN–SDC2–GFRA1 axis operates in mouse SSCs untested
    • Downstream pathway mediating GFRA1-dependent therapy resistance in GBM not defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the structural basis for how GFRA1 simultaneously engages RET and MCOLN1 through distinct mechanisms, how GPI-anchored GFRA1 accesses lysosomal MCOLN1, and whether RET-independent GFRA1 signaling contributes to normal enteric or renal development.
  • No high-resolution structure of GFRA1 in complex with MCOLN1
  • Membrane topology allowing GPI-anchored GFRA1 to reach lysosomal lumen unexplained
  • RET-independent signaling not tested in developmental contexts in vivo

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005764 lysosome 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3 R-HSA-9612973 Autophagy 3
Partners
GDNFMCOLN1RETSDC2SRCST3GAL1
Complex memberships
GDNF–GFRA1–RET ternary signaling complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 GFRA1 (GDNFR-alpha) is a GPI-linked cell surface receptor that binds GDNF specifically and mediates activation of the RET protein-tyrosine kinase; GDNF treatment of GFRA1-expressing cells rapidly stimulates RET autophosphorylation, and soluble GFRA1 can reconstitute RET activation in trans in cells lacking GFRA1, an effect blocked by soluble RET-Fc fusion protein, establishing a stepwise GDNF–GFRA1–RET signaling complex. Expression cloning, ligand-binding assays, RET autophosphorylation assays, soluble receptor reconstitution, Ret-Fc inhibition Cell High 8674117
2003 The first cadherin-like domain (CLD1) of RET, together with CLD2 and CLD3, forms an extended binding surface for the GDNF–GFRA1 complex; loss-of-function mutagenesis of CLD1 residues on one face of the molecular model abolished interaction with the GDNF–GFRA1 complex, and N-linked glycosylation of RET was not required for ligand binding. Homologue-scanning mutagenesis of human vs. Xenopus RET ectodomain chimeras, binding assays with GDNF–GFRA1 complex The Journal of biological chemistry High 14514671
2005 GFRA1 is highly selective for GDNF over artemin: cell-free binding studies showed weak artemin interaction only when soluble RET was present, and in GFRA1-transfected cells artemin did not compete with GDNF binding, did not induce ERK or AKT phosphorylation, was >10,000-fold less potent than GDNF at stimulating RET phosphorylation, and an anti-GFRA1 antibody blocked GDNF- but not artemin-mediated DRG neuron survival. Cell-free binding assays, competitive radioligand binding, ERK/AKT phosphorylation assays, RET phosphorylation assays, anti-GFRA1 antibody neutralization in primary neurons Biochemistry High 15709767
2007 Gfra1 knockdown in mouse type A spermatogonia via siRNA induced differentiation (elevated KIT expression, decreased POU5F1 and PCNA) and reduced RET phosphorylation, demonstrating that GFRA1 maintains spermatogonial stem cell self-renewal by sustaining RET kinase activity. siRNA knockdown, RET phosphorylation assay, colony-forming assay, marker expression by western blot/RT-PCR Biology of reproduction High 17625109
2003 GFRA1 undergoes efficient endocytosis (~30–40% of surface-bound ligand internalized within 2 min) in cells lacking RET, in a ligand-dependent manner; the presence of RET slows GFRA1 internalization at early time points, indicating distinct Ret-independent and Ret-dependent internalization mechanisms. Internalization assays in neuroblastoma and transfected fibroblast cell lines lacking RET, primary hippocampal neurons from transgenic mice with kinase-inactive RET Cellular and molecular neurobiology Medium 12701883
2016 GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by activating SRC phosphorylation and AMPK-dependent autophagy independent of RET kinase; cisplatin-resistant osteosarcoma cells show NFKB1-mediated GFRA1 upregulation, and GFRA1 expression promotes tumor growth in xenograft models that is reversed by autophagy inhibition. GFRA1 overexpression/knockdown, SRC and AMPK phosphorylation assays, autophagy flux assays, mouse xenograft models, NFκB pathway analysis Autophagy High 27754745
2018 GFRA1 is a substrate of ST3GAL1-mediated O-linked sialylation, which is required for GDNF-induced RET, AKT, and ERα phosphorylation in ER-positive breast cancer cells; GDNF induces ST3GAL1 transcription creating a positive feedback loop, and ST3GAL1 knockdown reduces GDNF-mediated cell proliferation. ST3GAL1 silencing, phosphorylation assays (RET, AKT, ERα), proliferation assays, transcriptional reporter assays Cancer letters Medium 30040982
2007 GDNF stimulation of RET+/GFRA1+ MCF7 breast cancer cells in vitro enhanced cell proliferation, survival, and cell scattering; in tumor xenografts, GDNF (from infiltrating fibroblasts) signals through RET and GFRA1 in a paracrine manner, and inflammatory cytokines TNF-α and IL-1β synergistically upregulate GDNF expression in fibroblasts and tumor cells. In vitro proliferation/survival/scattering assays with GDNF stimulation, xenograft GDNF expression analysis, cytokine treatment of fibroblasts/tumor cells Cancer research Medium 18089803
2000 Depolarisation causes a marked increase in GFRα-1 mRNA and decreased GFRα-2 mRNA in sympathetic, parasympathetic and sensory neurons via L-type Ca2+ channels, accompanied by increased responsiveness to GDNF and decreased responsiveness to neurturin, demonstrating activity-dependent regulation of GFRA1 expression that shifts neurotrophic factor responsiveness. Competitive RT-PCR of receptor mRNAs in cultured embryonic neurons under depolarizing KCl, L-type Ca2+ channel antagonists, survival assays with GDNF/neurturin Development (Cambridge, England) Medium 10704393
2018 Gfra1 hypomorphic mice with 70–80% reduction in GFRa1 expression develop Hirschsprung's disease and associated enterocolitis, with HAEC proceeding from goblet cell dysplasia with abnormal mucin production to epithelial damage; microbial adherence is a late event, establishing goblet cell dysfunction as a primary pathological mechanism downstream of reduced GFRA1 signaling. Gene targeting in mouse ES cells to generate Gfra1 hypomorphic mice, histopathology, disease progression analysis Cellular and molecular gastroenterology and hepatology High 30594740
2001 RET(Men2B) constitutively active transgene produces sympathoadrenal tumors independently of GDNF/GFRα1 stimulation, but does not rescue intestinal aganglionosis in gfra1(-/-) mice, indicating that GFRA1 is essential for enteric neural progenitor colonization of the gut upstream of or in parallel with constitutive RET activation. Genetic epistasis using RET(Men2B) transgene crossed into gfra1-null background, histopathology Pediatric and developmental pathology Medium 11779046
2020 Biallelic loss-of-function variants in GFRA1 (nonsense and frameshift) cause autosomal recessive bilateral renal agenesis in humans, consistent with GFRA1's role as a receptor on the Wolffian duct regulating ureteric bud outgrowth. Genome/exome sequencing, homozygosity mapping, Sanger confirmation in consanguineous families Journal of the American Society of Nephrology Medium 33020172
2023 ASH2L-dependent H3K4 trimethylation in the ureteric bud lineage acts as an upstream epigenetic regulator of Ret, Gfra1, and Wnt11 expression; UB-specific Ash2l inactivation reduces H3K4me3, slows UB tip cell proliferation, delays budding, and impairs branching morphogenesis. Conditional Ash2l knockout in mouse UB lineage, RNA-seq, CUT&Tag chromatin profiling, histopathology Journal of the American Society of Nephrology Medium 36758123
2016 LncRNA033862, an antisense transcript of Gfra1, interacts with Gfra1 chromatin and regulates Gfra1 expression levels in spermatogonial stem cells; lncRNA033862 knockdown severely impairs SSC survival and repopulation capacity. Global lncRNA expression profiling, chromatin interaction assays, lncRNA knockdown, SSC transplantation assay Cell death & disease Medium 26962690
2020 Small-molecule RET agonists (Q compounds) structurally derived from Q121 can activate RET in a GFRA1-dependent or GFRA1-independent manner depending on their structure; GFRα1 co-expression modulates RET-mediated AKT and ERK signaling in a biased manner, enhancing one pathway while diminishing another. Biochemical RET phosphorylation assays, AKT/ERK signaling assays in murine cells with/without GFRα1, retinal organotypic cultures, genetic mutant retinitis pigmentosa model The Journal of biological chemistry Medium 32245892
2022 The GDNF–GFRA1 axis activates autophagy flux in gastrointestinal stromal tumor cells via GFRA1 interaction with lysosomal calcium channel MCOLN1, activating Ca2+-dependent TFEB signaling that transcriptionally upregulates lysosome levels; this RET-independent mechanism promotes tumor dormancy and imatinib resistance. Loss- and gain-of-function studies in vitro and in vivo, co-IP of GFRA1 and MCOLN1, TFEB reporter assays, calcium signaling assays, rescue experiments Cancer letters Medium 35288241
2023 Tumor-associated macrophage-derived GDNF activates GFRA1 in gastric cancer cells to regulate lysosomal function and autophagy flux via Ca2+ signaling in a RET-independent manner, protecting tumor cells from apoptosis under metabolic stress and promoting liver metastasis. Loss- and gain-of-function studies in vitro and in vivo, cytosolic calcium ion signaling assays, rescue experiments with GDNF, autophagy flux assays Cellular oncology (Dordrecht, Netherlands) Medium 36808605
2024 GDNF/GFRA1 signaling contributes to chemoresistance and radioresistance in glioblastoma; CRISPR/Cas9 knockout of GFRA1 sensitized patient-derived glioblastoma spheroids to temozolomide, lomustine, and radiotherapy, and knockout of GDNF sensitized cells to chemotherapy in a manner fully reversed by exogenous GDNF. CRISPR/Cas9 knockout of GDNF and GFRA1 in patient-derived glioblastoma spheroid cultures, RNA-seq, qPCR, chemotherapy and irradiation survival assays, GDNF rescue Scientific reports Medium 39085346
2010 Histone H3 methylation and acetylation regulate Gfra1 gene expression in male germ cells; treatment with the HDAC inhibitor trichostatin A induced Gfra1 expression associated with gain of activating histone H3 methylation and acetylation at the Gfra1 promoter without changes in CpG DNA methylation. ChIP-qPCR for histone modifications at Gfra1 promoter, treatment with KDM1 inhibitor and HDAC inhibitor in GC-1 germ cell line, qPCR PloS one Medium 20856864
1999 Human GFRα-1 immunoreactivity is localized at the neuromuscular junction and myelinated peripheral nerves, while GFRα-1 mRNA is present in ventral horn spinal cord but not skeletal muscle, suggesting that GFRα-1 protein is transported anterogradely to the NMJ for GDNF uptake and internalization. Immunohistochemistry of human skeletal muscle, RT-PCR of spinal cord and muscle tissue Neuroscience letters Low 10821644
2024 PTN from Leydig cells signals through SDC2 in human spermatogonia to maintain GFRA1 expression; SDC2 knockdown downregulated GFRA1 and impaired SSC proliferation and PLZF expression, while exogenous PTN rescued proliferation and GFRA1 expression in SDC2 knockdown cells. Single-cell RNA-seq analysis, immunofluorescence, protein co-immunoprecipitation, SDC2 knockdown in human SSC lines, exogenous PTN rescue, transcriptome analysis Biological research Medium 39285301

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 1026 8674117
2017 circGFRA1 and GFRA1 act as ceRNAs in triple negative breast cancer by regulating miR-34a. Journal of experimental & clinical cancer research : CR 286 29037220
1997 Differential regulation of mRNAs for GDNF and its receptors Ret and GDNFR alpha after sciatic nerve lesion in the mouse. The European journal of neuroscience 219 9240402
1997 Neurturin and glial cell line-derived neurotrophic factor receptor-beta (GDNFR-beta), novel proteins related to GDNF and GDNFR-alpha with specific cellular patterns of expression suggesting roles in the developing and adult nervous system and in peripheral organs. The Journal of neuroscience : the official journal of the Society for Neuroscience 218 9334423
2007 Gfra1 silencing in mouse spermatogonial stem cells results in their differentiation via the inactivation of RET tyrosine kinase. Biology of reproduction 145 17625109
2016 GFRA1 promotes cisplatin-induced chemoresistance in osteosarcoma by inducing autophagy. Autophagy 133 27754745
2007 A role for glial cell derived neurotrophic factor induced expression by inflammatory cytokines and RET/GFR alpha 1 receptor up-regulation in breast cancer. Cancer research 122 18089803
1996 De novo mutation of GDNF, ligand for the RET/GDNFR-alpha receptor complex, in Hirschsprung disease. Human molecular genetics 119 8968758
2011 Distribution of GFRA1-expressing spermatogonia in adult mouse testis. Reproduction (Cambridge, England) 89 22143971
2000 Glial cell line-derived neurotrophic factor (GDNF) and its receptor (GFR-alpha 1) are strongly expressed in human gliomas. Acta neuropathologica 81 10672319
1997 Cloning, mRNA distribution and chromosomal localisation of the gene for glial cell line-derived neurotrophic factor receptor beta, a homologue to GDNFR-alpha. Human molecular genetics 81 9259272
1998 Glial cell line-derived neurotrophic factor/neurturin-induced differentiation and its enhancement by retinoic acid in primary human neuroblastomas expressing c-Ret, GFR alpha-1, and GFR alpha-2. Cancer research 59 9605760
2016 A long non-coding RNA interacts with Gfra1 and maintains survival of mouse spermatogonial stem cells. Cell death & disease 58 26962690
1998 Human GFRA1: cloning, mapping, genomic structure, and evaluation as a candidate gene for Hirschsprung disease susceptibility. Genomics 46 9545641
2003 Identification of a surface for binding to the GDNF-GFR alpha 1 complex in the first cadherin-like domain of RET. The Journal of biological chemistry 44 14514671
1997 Expression of the RET receptor tyrosine kinase and GDNFR-alpha in normal and leukemic human hematopoietic cells and stromal cells of the bone marrow microenvironment. Blood 43 9108413
2018 GFRA1: A Novel Molecular Target for the Prevention of Osteosarcoma Chemoresistance. International journal of molecular sciences 40 29617307
2018 Reciprocal feedback regulation of ST3GAL1 and GFRA1 signaling in breast cancer cells. Cancer letters 39 30040982
1999 Expression of GDNF and GDNFR-alpha mRNAs in muscles of patients with motor neuron diseases. Neurochemical research 36 10447463
2009 Efficient enrichment of undifferentiated GFR alpha 1+ spermatogonia from immature rat testis by magnetic activated cell sorting. Cell and tissue research 34 19434428
2005 Glial cell line-derived neurotrophic factor (GDNF) receptor alpha-1 (GFR alpha 1) is highly selective for GDNF versus artemin. Biochemistry 34 15709767
1998 Up-regulation of GDNFR-alpha and c-ret mRNA in facial motor neurons following facial nerve injury in the rat. Brain research. Molecular brain research 33 9582449
2002 Genetic analysis of RET, GFR alpha 1 and GDNF genes in Spanish families with multiple endocrine neoplasia type 2A. International journal of cancer 32 11979448
2009 Magnetic activated cell sorting allows isolation of spermatogonia from adult primate testes and reveals distinct GFRa1-positive subpopulations in men. Journal of medical primatology 31 20015158
1999 Investigation of germline GFR alpha-1 mutations in Hirschsprung disease. Journal of medical genetics 29 10204848
1999 Expression of GDNF receptor (RET and GDNFR-alpha) mRNAs in the spinal cord of patients with amyotrophic lateral sclerosis. Brain research 28 10023033
2014 Gdnf-Gfra1 pathway is expressed in a spermatogenetic-dependent manner and is regulated by Fsh in a fish testis. Biology of reproduction 27 25165121
2021 CircRNA GFRA1 promotes hepatocellular carcinoma progression by modulating the miR-498/NAP1L3 axis. Scientific reports 25 33431945
2017 An Anti-GDNF Family Receptor Alpha 1 (GFRA1) Antibody-Drug Conjugate for the Treatment of Hormone Receptor-Positive Breast Cancer. Molecular cancer therapeutics 25 29282299
2023 Tumor-associated macrophage-derived GDNF promotes gastric cancer liver metastasis via a GFRA1-modulated autophagy flux. Cellular oncology (Dordrecht, Netherlands) 24 36808605
2018 Gfra1 Underexpression Causes Hirschsprung's Disease and Associated Enterocolitis in Mice. Cellular and molecular gastroenterology and hepatology 24 30594740
1998 Molecular cloning and expression analysis of GFR alpha-3, a novel cDNA related to GDNFR alpha and NTNR alpha. Biochemical and biophysical research communications 24 9535755
2020 LncRNA SNHG15 contributes to doxorubicin resistance of osteosarcoma cells through targeting the miR-381-3p/GFRA1 axis. Open life sciences 23 33817274
2008 Development of satellite glia in mouse sympathetic ganglia: GDNF and GFR alpha 1 are not essential. Glia 22 18551627
1998 Mutational analysis of the GDNF/RET-GDNFR alpha signaling complex in a kindred with vesicoureteral reflux. Human genetics 22 9600247
2010 Epigenetic mechanisms regulate stem cell expressed genes Pou5f1 and Gfra1 in a male germ cell line. PloS one 20 20856864
1998 Expression of glial cell line-derived neurotrophic factor and GDNFR-alpha mRNAs in human peripheral neuropathies. Brain research 20 9853108
2004 Expression of GDNF and GFR alpha 1 in mouse taste bud cells. The Journal of comparative neurology 18 15389609
2001 Responsiveness to neurturin of subpopulations of embryonic rat spinal motoneuron does not correlate with expression of GFR alpha 1 or GFR alpha 2. Developmental dynamics : an official publication of the American Association of Anatomists 17 11241828
2000 GFR alpha-1 is expressed in parvalbumin GABAergic neurons in the hippocampus. Brain research 17 10986340
2020 Small-molecule agonists of the RET receptor tyrosine kinase activate biased trophic signals that are influenced by the presence of GFRa1 co-receptors. The Journal of biological chemistry 16 32245892
1999 Expression of human GFR alpha-1 (GDNF receptor) at the neuromuscular junction and myelinated nerves. Neuroscience letters 16 10821644
2022 The nerve-tumour regulatory axis GDNF-GFRA1 promotes tumour dormancy, imatinib resistance and local recurrence of gastrointestinal stromal tumours by achieving autophagic flux. Cancer letters 15 35288241
2020 Biallelic Pathogenic GFRA1 Variants Cause Autosomal Recessive Bilateral Renal Agenesis. Journal of the American Society of Nephrology : JASN 15 33020172
2010 GFR α-1 receptor expression in the aging nigrostriatal and mesoaccumbens pathways. Journal of neurochemistry 15 20731758
2018 Preclinical evaluation of a GFRA1 targeted antibody-drug conjugate in breast cancer. Oncotarget 14 29796165
2003 Internalization of glial cell-derived neurotrophic factor receptor GFR alpha 1 in the absence of the ret tyrosine kinase coreceptor. Cellular and molecular neurobiology 14 12701883
2002 Evaluation of germline sequence variants of GFRA1, GFRA2, and GFRA3 genes in a cohort of Spanish patients with sporadic medullary thyroid cancer. Thyroid : official journal of the American Thyroid Association 14 12490080
2025 Molecular mechanisms of GDNF/GFRA1/RET and PI3K/AKT/ERK signaling interplay in neuroprotection: Therapeutic strategies for treating neurological disorders. Neuropeptides 12 40101330
2022 LMX1B Activated Circular RNA GFRA1 Modulates the Tumorigenic Properties and Immune Escape of Prostate Cancer. Journal of immunology research 12 35832649
2020 LncRNA LINC00210 regulated radiosensitivity of osteosarcoma cells via miR-342-3p/GFRA1 axis. Journal of clinical laboratory analysis 11 32841458
2000 Depolarisation causes reciprocal changes in GFR(alpha)-1 and GFR(alpha)-2 receptor expression and shifts responsiveness to GDNF and neurturin in developing neurons. Development (Cambridge, England) 11 10704393
1998 Genomic structure and chromosomal localization of the human GDNFR-alpha gene. Oncogene 11 9482105
2023 ASH2L Controls Ureteric Bud Morphogenesis through the Regulation of RET/GFRA1 Signaling Activity in a Mouse Model. Journal of the American Society of Nephrology : JASN 8 36758123
2021 Biallelic loss-of-function variants of GFRA1 cause lethal bilateral renal agenesis. European journal of medical genetics 7 34737117
2006 [RET and GFRA1 germline polymorphisms in medullary thyroid cancer patients]. Molekuliarnaia biologiia 7 16813162
2024 PTN from Leydig cells activates SDC2 and modulates human spermatogonial stem cell proliferation and survival via GFRA1. Biological research 6 39285301
2001 RET(Men2B)-transgene produces sympathoadrenal tumors but does not prevent intestinal aganglionosis in gdnf-/- or gfr alpha-1(-/-) mice. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society 6 11779046
1999 Mutation and deletion analysis of GFR alpha-1, encoding the co-receptor for the GDNF/RET complex, in human brain tumours. British journal of cancer 6 10408842
2024 WTAP-mediated m6A modification of circ_0032463 promotes osteosarcoma progression by sponging miR-145-5p and regulating GFRA1 expression. Journal of biochemical and molecular toxicology 5 39243199
2003 [Expressions of GDNF, GDNFR alpha and Ret proteins in the brain of rats with seizures induced by pilocarpine]. Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences 5 12914250
2024 GDNF/GFRA1 signaling contributes to chemo- and radioresistance in glioblastoma. Scientific reports 4 39085346
2022 Missense Variants in GFRA1 and NPNT Are Associated with Congenital Anomalies of the Kidney and Urinary Tract. Genes 4 36292572
2000 Expression of GFR alpha-1, GFR alpha-2, and c-Ret mRNAs in rat adrenal gland. Journal of neurocytology 4 11428050
2016 Association Between RET (rs1800860) and GFRA1 (rs45568534, rs8192663, rs181595401, rs7090693, and rs2694770) Variants and Kidney Size in Healthy Newborns. Genetic testing and molecular biomarkers 3 27533506
2000 [The expression of glial cell derived neurotrophic factor and its receptor GDNFR-alpha and GDNFR-beta mRNA in spinal cord, brainstem and frontal cortex during morphine withdrawal in rats]. Zhonghua yi xue za zhi 3 11798749
1997 Assignment of mouse Gfra1, the homologue of a new human HSCR candidate gene, to the telomeric region of mouse chromosome 19. Cytogenetics and cell genetics 2 9465906
2025 Epigenetic Regulation of GFRA1 by Extracellular Vesicle lncRNA SOX9-AS1 Facilitates Breast Cancer Metastasis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 0 40526376
2003 [Expression and significance of GFR alpha 1 gene in the recovery spermatogenesis of mice]. Zhonghua nan ke xue = National journal of andrology 0 14727347