A p75(NTR) and Nogo receptor complex mediates repulsive signaling by myelin-associated glycoprotein

Nat Neurosci. 2002 Dec;5(12):1302-8. doi: 10.1038/nn975.

Abstract

Myelin-associated glycoprotein (MAG), an inhibitor of axon regeneration, binds with high affinity to the Nogo-66 receptor (NgR). Here we report that the p75 neurotrophin receptor (p75(NTR)) is a co-receptor of NgR for MAG signaling. In cultured human embryonic kidney (HEK) cells expressing NgR, p75(NTR) was required for MAG-induced intracellular Ca2+ elevation. Co-immunoprecipitation showed an association of NgR with p75(NTR) that can be disrupted by an antibody against p75(NTR) (NGFR5), and extensive coexpression was observed in the developing rat nervous system. Furthermore, NGFR5 abolished MAG-induced repulsive turning of Xenopus axonal growth cones and Ca2+ elevation, both in neurons and in NgR/p75(NTR)-expressing HEK cells. Thus we conclude that p75(NTR) is a co-receptor of NgR for MAG signaling and a potential therapeutic target for promoting nerve regeneration.

Publication types

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

MeSH terms

  • Animals
  • Calcium Signaling / drug effects
  • Calcium Signaling / genetics
  • Cell Differentiation / genetics
  • Cell Membrane / drug effects
  • Cell Membrane / genetics
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Central Nervous System / cytology
  • Central Nervous System / growth & development*
  • Central Nervous System / metabolism*
  • Embryo, Nonmammalian
  • Fetus
  • Growth Cones / drug effects
  • Growth Cones / metabolism*
  • Growth Cones / ultrastructure
  • Humans
  • Immunohistochemistry
  • Myelin Proteins / genetics
  • Myelin Proteins / metabolism*
  • Myelin-Associated Glycoprotein / metabolism*
  • Myelin-Associated Glycoprotein / pharmacology
  • Nerve Regeneration / drug effects
  • Nerve Regeneration / genetics*
  • Nogo Proteins
  • Rats
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / immunology
  • Receptors, Nerve Growth Factor / metabolism*
  • Xenopus

Substances

  • Myelin Proteins
  • Myelin-Associated Glycoprotein
  • Nogo Proteins
  • RTN4 protein, human
  • Receptor, Nerve Growth Factor
  • Receptors, Nerve Growth Factor
  • Rtn4 protein, rat