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.
Yamashita
Toshihide
T
Department of Anatomy and Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Tohyama
Masaya
M
D000209:Acute-Phase Proteins / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002460:Cell Line; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D020800:Receptor, Nerve Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D000209:Acute-Phase Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D018992:Myelin-Associated Glycoprotein; D020800:Receptor, Nerve Growth Factor; C010781:acute-phase protein rho; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors