Abstract
Neurturin (NTN) is a recently identified homologue of glial-cell-line-derived neurotrophic factor (GDNF). Both factors promote the survival of a variety of neurons, and GDNF is required for the development of the enteric nervous system and kidney. GDNF signals through a receptor complex consisting of the receptor tyrosine kinase Ret and a glycosyl-phosphatidylinositol (GPI)-linked receptor termed GDNFR-alpha. Here we report the cloning of a new GPI-linked receptor termed NTNR-alpha that is homologous with GDNFR-alpha and is widely expressed in the nervous system and other tissues. By using microinjection to introduce expression plasmids into neurons, we show that coexpression of NTNR-alpha with Ret confers a survival response to neurturin but not GDNF, and that coexpression of GDNFR-alpha with Ret confers a survival response to GDNF but not neurturin. Our findings indicate that GDNF and neurturin promote neuronal survival by signalling through similar multicomponent receptors that consist of a common receptor tyrosine kinase and a member of a GPI-linked family of receptors that determines ligand specificity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Blotting, Northern
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Cell Survival / drug effects
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Cells, Cultured
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Chick Embryo
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Cloning, Molecular
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Drosophila Proteins*
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Glycosylphosphatidylinositols / metabolism*
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Ligands
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Mice
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Molecular Sequence Data
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Nerve Growth Factors / metabolism
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Nerve Growth Factors / pharmacology*
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Nerve Tissue Proteins / metabolism
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Nerve Tissue Proteins / pharmacology
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Neurons / cytology*
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Neurons / metabolism
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Neurturin
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Nodose Ganglion / cytology
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Proto-Oncogene Proteins / chemistry
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases / chemistry
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Receptor Protein-Tyrosine Kinases / genetics
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Receptor Protein-Tyrosine Kinases / metabolism*
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Receptors, Cell Surface / chemistry
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Receptors, Cell Surface / genetics
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Receptors, Cell Surface / metabolism*
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Signal Transduction
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Superior Cervical Ganglion / cytology
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Superior Cervical Ganglion / metabolism
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Type C Phospholipases / metabolism
Substances
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Drosophila Proteins
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Gdnf protein, mouse
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Glial Cell Line-Derived Neurotrophic Factor
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Glial Cell Line-Derived Neurotrophic Factor Receptors
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Glycosylphosphatidylinositols
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Ligands
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Nerve Growth Factors
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Nerve Tissue Proteins
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Neurturin
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Nrtn protein, mouse
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Proto-Oncogene Proteins
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Receptors, Cell Surface
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Proto-Oncogene Proteins c-ret
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Receptor Protein-Tyrosine Kinases
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Ret protein, Drosophila
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Ret protein, mouse
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Type C Phospholipases
Associated data
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GENBANK/U90541
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GENBANK/U90542