Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex

Neuron. 1998 Dec;21(6):1291-302. doi: 10.1016/s0896-6273(00)80649-2.

Abstract

The glial cell line-derived neurotrophic factor (GDNF) ligands (GDNF, Neurturin [NTN], and Persephin [PSP]) signal through a multicomponent receptor system composed of a high-affinity binding component (GFRalpha1-GFRalpha4) and a common signaling component (RET). Here, we report the identification of Artemin, a novel member of the GDNF family, and demonstrate that it is the ligand for the former orphan receptor GFRalpha3-RET. Artemin is a survival factor for sensory and sympathetic neurons in culture, and its expression pattern suggests that it also influences these neurons in vivo. Artemin can also activate the GFRalpha1-RET complex and supports the survival of dopaminergic midbrain neurons in culture, indicating that like GDNF (GFRalpha1-RET) and NTN (GFRalpha2-RET), Artemin has a preferred receptor (GFRalpha3-RET) but that alternative receptor interactions also occur.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Newborn
  • Binding Sites
  • Cell Survival
  • Cells, Cultured
  • Cloning, Molecular
  • Drosophila Proteins*
  • Embryo, Mammalian
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Humans
  • Ligands
  • Mesencephalon / cytology
  • Mesencephalon / physiology*
  • Mice
  • Models, Chemical
  • Molecular Sequence Data
  • Nerve Growth Factors / chemistry
  • Nerve Growth Factors / physiology*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / physiology*
  • Neurons / cytology
  • Neurons / physiology*
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-ret
  • Rats
  • Rats, Sprague-Dawley
  • Receptor Protein-Tyrosine Kinases / physiology*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction / physiology*
  • Superior Cervical Ganglion / cytology
  • Superior Cervical Ganglion / physiology*

Substances

  • ARTN protein, human
  • Artn protein, mouse
  • Artn protein, rat
  • Drosophila Proteins
  • GDNF protein, human
  • GFRA1 protein, human
  • GFRA2 protein, human
  • GFRA3 protein, human
  • Gdnf protein, mouse
  • Gdnf protein, rat
  • Gfra1 protein, mouse
  • Gfra2 protein, mouse
  • Gfra2 protein, rat
  • Gfra3 protein, mouse
  • Gfra3 protein, rat
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Ligands
  • Nerve Growth Factors
  • Nerve Tissue Proteins
  • Proto-Oncogene Proteins
  • Recombinant Proteins
  • Proto-Oncogene Proteins c-ret
  • Receptor Protein-Tyrosine Kinases
  • Ret protein, Drosophila
  • Ret protein, mouse
  • Ret protein, rat

Associated data

  • GENBANK/AF109401
  • GENBANK/AF109402
  • GENBANK/AF115765