Molecular cloning, expression and tissue distribution of glial-cell-line-derived neurotrophic factor family receptor alpha-3 (GFRalpha-3)

Eur J Biochem. 1998 Feb 1;251(3):622-30. doi: 10.1046/j.1432-1327.1998.2510622.x.


Neurturin and glial-cell-line-derived neurotrophic factor (GDNF) promote the survival and maintenance of different types of neuronal cells and signal through a receptor complex composed of a ligand binding subunit, either GDNF family receptor alpha-1 (GFRalpha-1) or alpha-2 (GFRalpha-2), together with the cRET membrane-bound protein tyrosine kinase. We have cloned GFRalpha-3, a novel receptor belonging to the GFRalpha family, that is 35% identical by amino acid sequence to both GFRalpha-1 and GFRalpha-2. GFRalpha-3 is a protein composed of 400 amino acid residues with three potential N-linked glycosylation sites together with the features characteristic of a glycosyl-phosphatidylinositol-anchored membrane protein. The heterologous expression of a FLAG-tagged GFRalpha-3 in human embryonic kidney cells showed that the protein is bound to the cell surface via a glycosyl-PtdIns anchor and is glycosylated, with different glycoforms migrating on SDS/PAGE with apparent molecular masses ranging over 43-62 kDa. The gene for GFRalpha-3 was mapped to human chromosome 5 in a region (q31.1-q31.3) where several disease loci, growth factor and growth factor receptor genes have been localized. Using northern blot analysis or reverse-transcription PCR, GFRalpha-3 was shown to be expressed within the nervous system predominantly in the cerebellum and the spinal cord while in peripheral tissues GFRalpha-3 was found to be expressed mostly in the colon, small intestine, pancreas, heart, testis and prostate. Using a GFRalpha-3-specific [35S]cRNA[gammaS] probe, in situ hybridization histochemistry experiments confirmed the expression in the cerebellum.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Brain / metabolism*
  • Cell Line
  • Chromosome Mapping
  • Chromosomes, Human, Pair 5*
  • Cloning, Molecular
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Glycosylation
  • Glycosylphosphatidylinositols / metabolism
  • Humans
  • In Situ Hybridization
  • Kidney
  • Membrane Glycoproteins*
  • Molecular Sequence Data
  • Nerve Growth Factors*
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / metabolism
  • Nerve Tissue Proteins / pharmacology
  • Oligopeptides
  • Organ Specificity
  • Peptides
  • Polymerase Chain Reaction
  • Rats
  • Receptors, Cell Surface / biosynthesis*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics*
  • Receptors, Nerve Growth Factor*
  • Recombinant Fusion Proteins / biosynthesis
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Transfection


  • GDNF protein, human
  • GFRA3 protein, human
  • Gdnf protein, rat
  • Gfra3 protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Glycosylphosphatidylinositols
  • Membrane Glycoproteins
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Oligopeptides
  • Peptides
  • Receptors, Cell Surface
  • Receptors, Nerve Growth Factor
  • Recombinant Fusion Proteins
  • FLAG peptide