Molecular cloning and expression analysis of GFR alpha-3, a novel cDNA related to GDNFR alpha and NTNR alpha.

Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related to TGF-beta and are survival factors for sympathetic, sensory, and central nervous system neurons. GDNF transmits its signal primarily through a receptor complex containing the receptor tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor, GDNFR alpha. NTN utilizes a receptor complex system that consists of Ret and another GPI-linked receptor, NTNR alpha. We have identified a mouse cDNA, termed GFR alpha-3, that encodes a putative GPI-linked receptor. At the protein level, mouse GFR alpha-3 is 35% identical to mouse GDNFR alpha and 36% identical to mouse NTNR alpha. Northern blot analysis showed that GFR alpha-3 is expressed in fetal mouse heart, brain, lung, and kidney and adult heart. These results indicate that the tissue distribution of GFR alpha-3 mRNA is different from that of GDNFR alpha or NTNR alpha mRNA, and suggest that GFR alpha-3 may function in differentiation of embryonic cells expressing its mRNA.