Myelin-associated glycoprotein interacts with the Nogo66 receptor to inhibit neurite outgrowth

Neuron. 2002 Jul 18;35(2):283-90. doi: 10.1016/s0896-6273(02)00770-5.

Abstract

Myelin inhibitors of axonal regeneration, like Nogo and MAG, block regrowth after injury to the adult CNS. While a GPI-linked receptor for Nogo (NgR) has been identified, MAG's receptor is unknown. We show that MAG inhibits regeneration by interaction with NgR. Binding of and inhibition by MAG are lost if neuronal GPI-linked proteins are cleaved. Binding of MAG to NgR-expressing cells is GPI dependent and sialic acid independent. Conversely, NgR binds to MAG-expressing cells. MAG, but not a truncated MAG that binds neurons but does not inhibit regeneration, precipitates NgR from NgR-expressing cells, DRG, and cerebellar neurons. Importantly, NgR antibody, soluble NgR, or dominant-negative NgR each prevent inhibition of neurite outgrowth by MAG. Also, MAG and Nogo66 compete for binding to NgR. These results suggest redundancy in myelin inhibitors and indicate therapies for CNS injuries.

Publication types

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

MeSH terms

  • Animals
  • Animals, Newborn
  • Binding, Competitive / drug effects
  • Binding, Competitive / physiology
  • CHO Cells
  • Cell Membrane / metabolism
  • Cell Membrane / ultrastructure
  • Central Nervous System / cytology
  • Central Nervous System / growth & development*
  • Central Nervous System / injuries*
  • Cricetinae
  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols / metabolism
  • Growth Cones / metabolism
  • Growth Cones / ultrastructure
  • Growth Substances / metabolism
  • Immunohistochemistry
  • Myelin Proteins / metabolism
  • Myelin Sheath / metabolism
  • Myelin-Associated Glycoprotein / deficiency*
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Associated Glycoprotein / pharmacology
  • N-Acetylneuraminic Acid / metabolism
  • Nerve Fibers, Myelinated / metabolism*
  • Nerve Fibers, Myelinated / ultrastructure
  • Nerve Regeneration / physiology*
  • Neurites / metabolism*
  • Neurites / ultrastructure
  • Nogo Receptor 1
  • Peptide Fragments / metabolism
  • Protein Binding / physiology
  • Rats
  • Receptors, Cell Surface / metabolism*

Substances

  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols
  • Growth Substances
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • NEPI-40 protein, rat
  • Nogo Receptor 1
  • Peptide Fragments
  • Receptors, Cell Surface
  • Rtn4r protein, rat
  • N-Acetylneuraminic Acid