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)(14) is a potent neu rotrophic factor with diverse biological functions.(3,8,10,16,19,20,22 ) Signal transduction of GDNF is mediated by binding to a glycosylphos phatidylinositol (GPI)-linked receptor GDNFR-alpha and activation of c -RET tyrosine kinase.(5,11,23,24) The recent discovery of a new GDNF h omolog neurturin(13) raises the possibility that multiple receptors ex ist for the members in the GDNF family, Here we report isolation of th e gene encoding a new receptor called GDNFR-beta. Sequence analysis in dicated that GDNFR-beta is also a GPI-linked protein, with 47% identit y to GDNFR-alpha. The GDNFR-beta transcript was preferentially express ed in the brain, spleen and lung, but moderate levels of GDNFR-beta mR NA mere 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 su perior colliculus, and zona inserta. A laminar pattern of expression w as detected in laver III of the cortex, Treatment with GDNF of PC12 ce lls transfected with the GDNFR-beta gene activated mitogen-activated p rotein kinase (MAPK) and elicited neurite outgrowth, GDNFR-alpha and G DNFR-beta together form a new family of GPI-linked receptors for GDNF- like molecules. (C) 1997 Published by Elsevier Science Ltd.