The p75 receptor transduces the signal from myelin-associated glycoprotein to Rho.
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.
Yamashita
Toshihide
T
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan. tyama@anat2.med.osaka-u.ac.jp
Higuchi
Haruhisa
H
Tohyama
Masaya
M
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism; D016501:Neurites / Q000378:metabolism* / Q000648:ultrastructure; D020800:Receptor, Nerve Growth Factor / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology*; D020741:rho GTP-Binding Proteins / Q000378:metabolism*
D005732:Gangliosides; D018992:Myelin-Associated Glycoprotein; D020800:Receptor, Nerve Growth Factor; C016481:trisialoganglioside GT1; D020741:rho GTP-Binding Proteins