Abstract
Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. The receptor for MAG or signals that elicit morphological changes in neurons remained to be established. Here we show that the neurotrophin receptor p75 (p75(NTR)) is the signal transducing element for MAG. Adult dorsal root ganglion neurons or postnatal cerebellar neurons from mice carrying a mutation in the p75(NTR) gene are insensitive to MAG with regard to neurite outgrowth. MAG activates small GTPase RhoA, leading to retarded outgrowth when p75(NTR)) is present. Colocalization of p75(NTR) and MAG binding is seen in neurons. Ganglioside GT1b, which is one of the binding partners of MAG, specifically associates with p75(NTR). Thus, p75(NTR) and GT1b may form a receptor complex for MAG to transmit the inhibitory signals in neurons.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding Sites / physiology
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Cell Differentiation / physiology*
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Cell Membrane / metabolism*
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Cell Membrane / ultrastructure
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Cells, Cultured
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Cerebellum / cytology
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Cerebellum / growth & development
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Cerebellum / metabolism
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Ganglia, Spinal / cytology
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Ganglia, Spinal / growth & development
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Ganglia, Spinal / metabolism
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Gangliosides / metabolism
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Mice
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Mice, Knockout
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Mutation / physiology
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Myelin-Associated Glycoprotein / metabolism*
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Nervous System / cytology
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Nervous System / growth & development*
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Nervous System / metabolism
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Neurites / metabolism*
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Neurites / ultrastructure
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Receptor, Nerve Growth Factor / deficiency*
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Receptor, Nerve Growth Factor / genetics
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Signal Transduction / physiology*
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rho GTP-Binding Proteins / metabolism*
Substances
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Gangliosides
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Myelin-Associated Glycoprotein
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Receptor, Nerve Growth Factor
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trisialoganglioside GT1
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rho GTP-Binding Proteins