title: Structural features of the Nogo receptor signaling complexes at the neuron/myelin interface.
abstract: Upon spinal cord injury, the central nervous system axons are unable to regenerate, partially due to the repulsive action of myelin inhibitors, such as the myelin-associated glycoprotein (MAG), Nogo-A and the oligodendrocyte myelin glycoprotein (OMgp). These inhibitors bind and signal through a single receptor/co-receptor complex that comprises of NgR1/LINGO-1 and either p75 or TROY, triggering intracellular downstream signaling that impedes the re-growth of axons. Structure-function analysis of myelin inhibitors and their neuronal receptors, particularly the NgRs, have provided novel information regarding the molecular details of the inhibitor/receptor/co-receptor interactions. Structural and biochemical studies have revealed the architecture of many of these proteins and identified the molecular regions important for assembly of the inhibitory signaling complexes. It was also recently shown that gangliosides, such as GT1b, mediate receptor/co-receptor binding. In this review, we highlight these studies and summarize our current understanding of the multi-protein cell-surface complexes mediating inhibitory signaling events at the neuron/myelin interface.
authors: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Electronic address: sahan@mskcc.org.
authors: Nayanendu
authors: N
authors: Saha
authors: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Electronic address: nikolovd@mskcc.org.
authors: Momchil
authors: M
authors: Kolev
authors: Structural Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Electronic address: momchil6666@gmail.com.
authors: Dimitar B
authors: DB
authors: Nikolov
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009185:Myelin Proteins / Q000737:chemistry* / Q000378:metabolism*; D009186:Myelin Sheath / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D000070817:Nogo Receptor 2; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D015398:Signal Transduction; D013119:Spinal Cord Injuries / Q000378:metabolism
chemical_list: D058851:GPI-Linked Proteins; C482293:LINGO1 protein, human; C115082:MAG protein, human; D008565:Membrane Proteins; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D000070817:Nogo Receptor 2; C560528:OMG protein, human; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; C474327:RTN4RL2 protein, human; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; C411850:TNFRSF19 protein, human
keywords: Chondroitin sulfate; Ganglioside; LINGO-1; Myelin associated glycoprotein; Nogo receptor; NogoA