Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex.
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.
Baloh
R H
RH
Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Tansey
M G
MG
Lampe
P A
PA
Fahrner
T J
TJ
Enomoto
H
H
Simburger
K S
KS
Leitner
M L
ML
Araki
T
T
Johnson
E M
EM
Milbrandt
J
J
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001665:Binding Sites; D002470:Cell Survival; D002478:Cells, Cultured; D003001:Cloning, Molecular; D029721:Drosophila Proteins; D004622:Embryo, Mammalian; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D008024:Ligands; D008636:Mesencephalon / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008956:Models, Chemical; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000737:chemistry / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology*
C490886:ARTN protein, human; C116599:Artn protein, mouse; C490887:Artn protein, rat; D029721:Drosophila Proteins; C495039:GDNF protein, human; C494987:GFRA1 protein, human; C494990:GFRA2 protein, human; C494993:GFRA3 protein, human; C495040:Gdnf protein, mouse; C495041:Gdnf protein, rat; C494988:Gfra1 protein, mouse; C494991:Gfra2 protein, mouse; C494992:Gfra2 protein, rat; C494994:Gfra3 protein, mouse; C494995:Gfra3 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse; C495001:Ret protein, rat