title: Suppression of the p75 receptor signal attenuates the effect of ephrin-B3 and promotes axonal regeneration of the injured optic nerve.
abstract: The p75 neurotrophin receptor (p75NTR) is known to transduce the signal from some myelin-associated axon growth inhibitors, including Nogo and myelin-associated glycoprotein. As ephrin-B3, a member of the ephrin family, is also expressed in myelin and inhibits axon growth, the purpose of this study was to assess the possible involvement of p75NTR in ephrin-B3 signaling. Here, we report that p75NTR is required for the inhibitory effect of ephrin-B3 on neurite growth in vitro. While ephrin-B3 inhibited neurite elongation of embryonic cortical neurons, the neurons with p75NTR knockdown or with EphA4 knockdown were less sensitive to ephrin-B3. Although no direct interaction of p75NTR with ephrin-B3 was observed, Pep5, a peptide that specifically inhibits RhoA activation mediated by p75NTR, reduced the effect of ephrin-B3. Therefore, p75NTR functions as a signal transducer for ephrin-B3. Moreover, axonal regeneration in vivo was induced by Pep5 application after optic nerve crush injury in mice. Thus, Pep5 is a promising agent that contributes to axonal regeneration in the central nervous system.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Uesugi
authors.forename: Y
authors.initials: Y
authors.lastname: Kimura
authors.forename: T
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D036389:Ephrin-B3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D009416:Nerve Regeneration / Q000187:drug effects* / Q000235:genetics; D016501:Neurites / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009900:Optic Nerve / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000188:drug therapy / Q000196:embryology / Q000235:genetics*; D010455:Peptides / Q000494:pharmacology*; D017475:Receptors, Nerve Growth Factor / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D020741:rho GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D020742:rhoA GTP-Binding Protein
chemical_list: D004791:Enzyme Inhibitors; D036389:Ephrin-B3; D010455:Peptides; D017475:Receptors, Nerve Growth Factor; C517634:Ngfr protein, mouse; C526380:RhoA protein, mouse; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein