Binding of Soluble Myelin-Associated Glycoprotein to Specific Gangliosides Induces the Association of p75NTR to Lipid Rafts and Signal Transduction

J Neurochem. 2005 Jul;94(1):15-21. doi: 10.1111/j.1471-4159.2005.03121.x.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Chick Embryo
  • Gangliosides / metabolism*
  • Gangliosides / physiology
  • Membrane Microdomains / metabolism*
  • Membrane Microdomains / physiology
  • Mice
  • Mice, Knockout
  • Myelin-Associated Glycoprotein / metabolism*
  • Myelin-Associated Glycoprotein / physiology
  • Protein Binding / physiology
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor / metabolism*
  • Receptors, Nerve Growth Factor / physiology
  • Signal Transduction / physiology*
  • Solubility

Substances

  • Gangliosides
  • Myelin-Associated Glycoprotein
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor