title: Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75NTR to lipid rafts and signal transduction.
abstract: Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. Here we show that gangliosides, GT1b and GD1a, as well as the Nogo receptor, are functional binding partners for soluble MAG-Fc. Postnatal cerebellar neurons from mice deficient in the GalNAcT gene are insensitive to MAG with regard to neurite outgrowth and lack in the activation of RhoA. MAG-Fc or the antibody to GT1b and GD1a elicits recruitment of p75(NTR.) to lipid rafts, specialized microdomain for signal transduction. Disruption of lipid rafts results in abolishment of inhibitory effects of MAG-Fc and the Nogo peptide. These findings establish gangliosides as functional binding partners for soluble MAG. Gangliosides may play a role in translocation of p75(NTR.) to lipid rafts for initiation of the signal transduction.
authors.affiliation: Department of Neurobiology, Graduate School of Medicine, Chiba University, Inohana, Chuo-ku, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Fujitani
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Kawai
authors.forename: Richard L
authors.initials: RL
authors.lastname: Proia
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yasuda
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D005732:Gangliosides / Q000378:metabolism* / Q000502:physiology; D021962:Membrane Microdomains / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism* / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D012995:Solubility
chemical_list: D005732:Gangliosides; D018992:Myelin-Associated Glycoprotein; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor