Glial cell line-derived neurotrophic factor (GDNF) and the related neurotrophic factor neurturin (NTN) are potent survival factors for central and peripheral neurons. GDNF is a glycosylated, disulfide-bonded homodimer that is distantly related to the TGFbeta superfamily of growth factors. Three receptors for these factors, GFRalpha-1 (also designated GDNFR-alpha, RETL1 or TrnR-1), GFRalpha-2 (also designated GDNFR-beta, RETL2, NTNR-alpha or TrnR-2) and GFRalpha-3 have been identified. The receptors do not contain transmembrane domains and are attached to the cell membrane by glycosyl-phosphoinositol linkage. Both GFRalpha-1 and GFRalpha-2 have been shown to mediate the GDNF-dependent and NTN-dependent phosphorylation and activation of the tyrosine kinase Ret. GFRalpha-3 is expressed only during development.
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