Glial cell line-derived neurotrophic factor (GDNF) and the related neurotrophic factor neurturin (NTN) are potent survival factors for central and peripheral neurons. Receptors for these factors include GFRalpha-1 (previously designated GDNFR-alpha), GFRalpha-2 (also designated RETL2), GFRalpha-3 and GFRalpha-4 (also known as persephin receptor). The receptors do not contain transmembrane domains and are attached to the cell membrane by glycosylphosphoinositol linkage. Binding of GDNF or NTN to one of these receptors leads to the activation of the tyrosine kinase Ret. GFRalpha-4 mediates the activation and GDNF-induced autophosphorylation of the RET receptor. It is mainly expressed in the adult thyroid gland, but lower levels may also be detected in fetal adrenal and thyroid glands.
