title: GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor family.
abstract: GDNF, neurturin, and persephin are transforming growth factor beta-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 alpha components 1 and 2, GFRalpha1 or GFRalpha2), whereas the receptor for persephin is unknown. Herein we describe a third member of the GF coreceptor family called GFRalpha3 that is encoded by a gene located on human chromosome 5q31.2-32. GFRalpha3 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. GFRalpha3 is also expressed at high levels in developing, but not adult, peripheral nerve. GFRalpha3 is a glycoprotein that is glycosyl-phosphatidylinositol-linked to the cell surface like GFRalpha1 and GFRalpha2. Fibroblasts expressing Ret and GFRalpha3 do not respond to any of the known members of the GDNF family, suggesting that GFRalpha3 interacts with an unknown ligand or requires a different or additional signaling protein to function.
authors.affiliation: Department of Pathology and Internal Medicine, Molecular Biology, and Pharmacology, Washington University School of Medicine, 660 South Euclid Avenue, Box 8118, St. Louis, MO 63110, USA.
authors.forename: R H
authors.initials: RH
authors.lastname: Baloh
authors.forename: A
authors.initials: A
authors.lastname: Gorodinsky
authors.forename: J P
authors.initials: JP
authors.lastname: Golden
authors.forename: M G
authors.initials: MG
authors.lastname: Tansey
authors.forename: C L
authors.initials: CL
authors.lastname: Keck
authors.forename: N C
authors.initials: NC
authors.lastname: Popescu
authors.forename: E M
authors.initials: EM
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Milbrandt
mesh_terms: D016475:3T3 Cells; D000328:Adult; D000595:Amino Acid Sequence; D000818:Animals; D002874:Chromosome Mapping; D005347:Fibroblasts / Q000378:metabolism; D005724:Ganglia / Q000378:metabolism; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D006801:Humans; D017403:In Situ Hybridization; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000302:isolation & purification*; D051379:Mice; D008969:Molecular Sequence Data; D009414:Nerve Growth Factors / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000378:metabolism*; D051101:Neurturin; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification*; D017475:Receptors, Nerve Growth Factor; D016415:Sequence Alignment; D015398:Signal Transduction; D014162:Transfection
chemical_list: C495039:GDNF protein, human; C495040:Gdnf protein, mouse; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008562:Membrane Glycoproteins; C495053:NRTN protein, human; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495056:Nrtn protein, mouse; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; C110758:persephin