Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRα3-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 (GFR alpha 1-GFR alpha 4) 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 GFR alpha 3-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 GFR alpha 1-RET complex and supports the survival of dopaminergic midbrain neurons in culture, indicating that like GDNF (GFR alpha 1-RET) and NTN (GFR alpha 2-RET), Artemin has a preferred receptor (GFR alpha 3-RET) but that alternative receptor interactions also occur.