P75 interacts with the Nogo receptor as a co-receptor for Nogo, MAG and OMgp.
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.
Wang
Kevin C
KC
Division of Neuroscience, Children's Hospital and Program in Neuroscience, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts 02115, USA.
Kim
Jieun A
JA
Sivasankaran
Rajeev
R
Segal
Rosalind
R
He
Zhigang
Z
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
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