Cloning and characterization of glial cell line-derived neurotrophic factor receptor-B: A novel receptor for members of glial cell line-derived neurotrophic factor family of neurotrophic factors

Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with diverse biological functions. Signal transduction of GDNF is mediated by binding to a glycosylphosphatidylinositol (GPI)-linked receptor GDNFR-α and activation of c-RET tyrosine kinase. The recent discovery of a new GDNF homolog neurturin raises the possibility that multiple receptors exist for the members in the GDNF family. Here we report isolation of the gene encoding a new receptor called GDNFR-β. Sequence analysis indicated that GDNFR-β is also a GPI-linked protein, with 47% identity to GDNFR-α. The GDNFR-β transcript was preferentially expressed in the brain, spleen and lung, but moderate levels of GDNFR-β mRNA were also found in kidney and the entire gastrointestinal track. In situ hybridization revealed high expression levels in the entorhinal cortex and olfactory bulb, followed by cortex, septum, inferior and superior colliculus, and zona inserta. A laminar pattern of expression was detected in layer III of the cortex. Treatment with GDNF of PC12 cells transfected with the GDNFR-β gene activated mitogeo-activated protein kinase (MAPK) and elicited neurite outgrowth. GDNFR-α and GDNFR-β together form a new family of GPI-linked receptors for GDNF-like molecules.