Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor

Science. 2002 Aug 16;297(5584):1190-3. doi: 10.1126/science.1073031. Epub 2002 Jun 27.

Abstract

Axonal regeneration in the adult central nervous system (CNS) is limited by two proteins in myelin, Nogo and myelin-associated glycoprotein (MAG). The receptor for Nogo (NgR) has been identified as an axonal glycosyl-phosphatidyl-inositol (GPI)-anchored protein, whereas the MAG receptor has remained elusive. Here, we show that MAG binds directly, with high affinity, to NgR. Cleavage of GPI-linked proteins from axons protects growth cones from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of neurite outgrowth. MAG-resistant embryonic neurons are rendered MAG-sensitive by expression of NgR. MAG and Nogo-66 activate NgR independently and serve as redundant NgR ligands that may limit axonal regeneration after CNS injury.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Axons / physiology*
  • Binding Sites
  • COS Cells
  • Chick Embryo
  • Cloning, Molecular
  • GPI-Linked Proteins
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / embryology
  • Ganglia, Spinal / metabolism
  • Gene Library
  • Ligands
  • Mice
  • Myelin Proteins / chemistry
  • Myelin Proteins / metabolism
  • Myelin Proteins / pharmacology
  • Myelin-Associated Glycoprotein / chemistry
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Associated Glycoprotein / metabolism*
  • Nerve Regeneration
  • Neurites / physiology*
  • Neurons / metabolism
  • Nogo Proteins
  • Nogo Receptor 1
  • Peptide Fragments / metabolism
  • Peptide Fragments / pharmacology
  • Phosphatidylinositol Diacylglycerol-Lyase
  • Protein Structure, Tertiary
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / metabolism
  • Sialic Acids / metabolism
  • Transfection
  • Type C Phospholipases / metabolism

Substances

  • GPI-Linked Proteins
  • Ligands
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • NEPI-40 protein, mouse
  • Nogo Proteins
  • Nogo Receptor 1
  • Peptide Fragments
  • Receptors, Cell Surface
  • Recombinant Fusion Proteins
  • Rtn4 protein, mouse
  • Rtn4 protein, rat
  • Rtn4r protein, mouse
  • Rtn4r protein, rat
  • Sialic Acids
  • Type C Phospholipases
  • Phosphatidylinositol Diacylglycerol-Lyase