Molecular Cloning and Expression Analysis of GFRα-3, a Novel cDNA Related to GDNFRα and NTNRα

Abstract Glial-cell-line-derived neurotrophic factor (GDNF) and neurturin (NTN) are structurally related to TGF-β 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, GDNFRα. NTN utilizes a receptor complex system that consists of Ret and another GPI-linked receptor, NTNRα. We have identified a mouse cDNA, termed GFRα-3, that encodes a putative GPI-linked receptor. At the protein level, mouse GFRα-3 is 35% identical to mouse GDNFRα and 36% identical to mouse NTNRα. Northern blot analysis showed that GFRα-3 is expressed in fetal mouse heart, brain, lung, and kidney and adult heart. These results indicate that the tissue distribution of GFRα-3 mRNA is different from that of GDNFRα or NTNRα mRNA, and suggest that GFRα-3 may function in differentiation of embryonic cells expressing its mRNA.