LINGO-1 is a component of the Nogo-66 receptor/p75 signaling complex

Nat Neurosci. 2004 Mar;7(3):221-8. doi: 10.1038/nn1188. Epub 2004 Feb 15.

Abstract

Axon regeneration in the adult CNS is prevented by inhibitors in myelin. These inhibitors seem to modulate RhoA activity by binding to a receptor complex comprising a ligand-binding subunit (the Nogo-66 receptor NgR1) and a signal transducing subunit (the neurotrophin receptor p75). However, in reconstituted non-neuronal systems, NgR1 and p75 together are unable to activate RhoA, suggesting that additional components of the receptor may exist. Here we describe LINGO-1, a nervous system-specific transmembrane protein that binds NgR1 and p75 and that is an additional functional component of the NgR1/p75 signaling complex. In non-neuronal cells, coexpression of human NgR1, p75 and LINGO-1 conferred responsiveness to oligodendrocyte myelin glycoprotein, as measured by RhoA activation. A dominant-negative human LINGO-1 construct attenuated myelin inhibition in transfected primary neuronal cultures. This effect on neurons was mimicked using an exogenously added human LINGO-1-Fc fusion protein. Together these observations suggest that LINGO-1 has an important role in CNS biology.

MeSH terms

  • Amino Acid Sequence / genetics
  • Animals
  • Animals, Newborn
  • Astrocytes / metabolism
  • Axons / metabolism
  • Base Sequence / genetics
  • Cells, Cultured
  • DNA, Complementary / analysis
  • DNA, Complementary / genetics
  • Fetus
  • GPI-Linked Proteins
  • Humans
  • Macromolecular Substances
  • Membrane Proteins / genetics
  • Membrane Proteins / isolation & purification
  • Membrane Proteins / metabolism*
  • Molecular Sequence Data
  • Mutation / genetics
  • Myelin Proteins / metabolism*
  • Myelin Sheath / metabolism
  • Myelin-Associated Glycoprotein / genetics
  • Myelin-Associated Glycoprotein / isolation & purification
  • Myelin-Associated Glycoprotein / metabolism*
  • Myelin-Oligodendrocyte Glycoprotein
  • Nerve Regeneration / physiology*
  • Nerve Tissue Proteins
  • Nogo Receptor 1
  • Protein Structure, Tertiary / genetics
  • Rats
  • Receptor, Nerve Growth Factor
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / isolation & purification
  • Receptors, Cell Surface / metabolism*
  • Receptors, Nerve Growth Factor / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / genetics
  • rhoA GTP-Binding Protein / metabolism

Substances

  • DNA, Complementary
  • GPI-Linked Proteins
  • LINGO1 protein, human
  • MOG protein, human
  • Macromolecular Substances
  • Membrane Proteins
  • Mog protein, rat
  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Myelin-Oligodendrocyte Glycoprotein
  • Nerve Tissue Proteins
  • Nogo Receptor 1
  • OMG protein, human
  • Omg protein, rat
  • RTN4R protein, human
  • Receptor, Nerve Growth Factor
  • Receptors, Cell Surface
  • Receptors, Nerve Growth Factor
  • Recombinant Fusion Proteins
  • Rtn4r protein, rat
  • rhoA GTP-Binding Protein