GDNF, neurturin, and persephin are transforming growth factor β- related neurotrophic factors known collectively as the GDNF family (GF). GDNF and neurturin signal through a multicomponent receptor complex containing a signaling component (the Ret receptor tyrosine kinase) and either of two glycosyl-phosphatidylinositol-linked binding components (GDNF family receptor α components 1 and 2, GFRα1 or GFRα2), whereas the receptor for persephin is unknown. Herein we describe a third member of the GF coreceptor family called GFRα3 that is encoded by a gene located on human chromosome 5q31.2- 32. GFRα3 is not expressed in the central nervous system of the developing or adult animal but is highly expressed in several developing and adult sensory and sympathetic ganglia of the peripheral nervous system. GFRα3 is also expressed at high levels in developing, but not adult, peripheral nerve. GFRα3 is a glycoprotein that is glycosyl-phosphatidylinositol-linked to the cell surface like GFRα1 and GFRα2. Fibroblasts expressing Ret and GFRα3 do not respond to any of the known members of the GDNF family, suggesting that GFRα3 interacts with an unknown ligand or requires a different or additional signaling protein to function.

Original languageEnglish
Pages (from-to)5801-5806
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number10
StatePublished - May 12 1998


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