GFRalpha-4, a new GDNF family receptor.

GFRalpha-1, GFRalpha-2, and GFRalpha-3 constitute a family of structurally related, glycosyl-phosphatidylinosital-linked, cell surface proteins, two of which, GFRalpha-1 and GFRalpha-2, are components of the receptor complex for the neurotrophic factors GDNF and neurturin, respectively. By screening an embryonic chicken brain cDNA library with a GFRalpha-1 probe at low stringency, we isolated cDNAs encoding an additional member of the GFRalpha family, GFRalpha-4. The nucleotide sequence predicts a 431-amino-acid secreted protein that is more closely related to GFRalpha-1 and GFRalpha-2 than to GFRalpha-3. GFRalpha-4 mRNA is expressed in distinctive patterns in the brain and several other organs and tissues of the chicken embryo. Our findings extend the family of GFRalpha proteins and provide information about the tissues in which GFRalpha-4 may function during development.