title: P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp.
abstract: In inhibiting neurite outgrowth, several myelin components, including the extracellular domain of Nogo-A (Nogo-66), oligodendrocyte myelin glycoprotein (OMgp) and myelin-associated glycoprotein (MAG), exert their effects through the same Nogo receptor (NgR). The glycosyl phosphatidylinositol (GPI)-anchored nature of NgR indicates the requirement for additional transmembrane protein(s) to transduce the inhibitory signals into the interior of responding neurons. Here, we demonstrate that p75, a transmembrane protein known to be a receptor for the neurotrophin family of growth factors, specifically interacts with NgR. p75 is required for NgR-mediated signalling, as neurons from p75 knockout mice are no longer responsive to myelin and to each of the known NgR ligands. Blocking the p75-NgR interaction also reduces the activities of these inhibitors. Moreover, a truncated p75 protein lacking the intracellular domain, when overexpressed in primary neurons, attenuates the same set of inhibitory activities, suggesting that p75 is a signal transducer of the NgR-p75 receptor complex. Thus, interfering with p75 and its downstream signalling pathways may allow lesioned axons to overcome most of the inhibitory activities associated with central nervous system myelin.
authors.affiliation: Division of Neuroscience, Children's Hospital and Program in Neuroscience, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
authors.forename: Kevin C
authors.initials: KC
authors.lastname: Wang
authors.forename: Jieun A
authors.initials: JA
authors.lastname: Kim
authors.forename: Rajeev
authors.initials: R
authors.lastname: Sivasankaran
authors.forename: Rosalind
authors.initials: R
authors.lastname: Segal
authors.forename: Zhigang
authors.initials: Z
authors.lastname: He
mesh_terms: D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D002642:Chick Embryo; D006224:Cricetinae; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism*; D063308:Myelin-Oligodendrocyte Glycoprotein; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011233:Precipitin Tests; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D058851:GPI-Linked Proteins; C571326:MOG protein, human; C571327:Mog protein, mouse; C571328:Mog protein, rat; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C560528:OMG protein, human; C560529:Omg protein, mouse; C560532:Omg protein, rat; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C419790:Rtn4r protein, mouse; C486581:Rtn4r protein, rat; D020932:Nerve Growth Factor