The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI

Nat Neurosci. 2003 May;6(5):461-7. doi: 10.1038/nn1045.


The neurotrophin receptor p75(NTR) is involved in the regulation of axonal elongation by neurotrophins as well as several myelin components, including Nogo, myelin-associated glycoprotein (MAG) and myelin oligodendrocyte glycoprotein (OMgp). Neurotrophins stimulate neurite outgrowth by inhibiting Rho activity, whereas myelin-derived proteins activate RhoA and thereby inhibit growth. Here we show that direct interaction of the Rho GDP dissociation inhibitor (Rho-GDI) with p75(NTR) initiates the activation of RhoA, and this interaction between p75(NTR) and Rho-GDI is strengthened by MAG or Nogo. We also found that p75(NTR) facilitates the release of prenylated RhoA from Rho-GDI. The peptide ligand that is associated with the fifth alpha helix of p75(NTR) inhibits the interaction between Rho-GDI and p75(NTR), thus silencing the action mediated by p75(NTR). This peptide has potential as a therapeutic agent against the inhibitory cues that block regeneration in the central nervous system.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / biosynthesis*
  • Acute-Phase Proteins / genetics
  • Animals
  • Cell Line
  • Ganglia, Spinal / cytology
  • Ganglia, Spinal / metabolism
  • Gene Expression Regulation / physiology
  • Guanine Nucleotide Dissociation Inhibitors / biosynthesis*
  • Guanine Nucleotide Dissociation Inhibitors / genetics
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Associated Glycoprotein / metabolism
  • Neurites / metabolism
  • Receptor, Nerve Growth Factor / biosynthesis*
  • Receptor, Nerve Growth Factor / genetics
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors


  • Acute-Phase Proteins
  • Guanine Nucleotide Dissociation Inhibitors
  • Myelin-Associated Glycoprotein
  • Receptor, Nerve Growth Factor
  • acute-phase protein rho
  • rho-Specific Guanine Nucleotide Dissociation Inhibitors