The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI
Copyright policy )The p75 receptor acts as a displacement factor that releases Rho from Rho-GDI
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.
- Osaka University Japan
Receptor, Nerve Growth Factor, Cell Line, Mice, Inbred C57BL, Mice, Myelin-Associated Glycoprotein, Gene Expression Regulation, Ganglia, Spinal, Neurites, Animals, Humans, rho-Specific Guanine Nucleotide Dissociation Inhibitors, Acute-Phase Proteins, Guanine Nucleotide Dissociation Inhibitors
Receptor, Nerve Growth Factor, Cell Line, Mice, Inbred C57BL, Mice, Myelin-Associated Glycoprotein, Gene Expression Regulation, Ganglia, Spinal, Neurites, Animals, Humans, rho-Specific Guanine Nucleotide Dissociation Inhibitors, Acute-Phase Proteins, Guanine Nucleotide Dissociation Inhibitors
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