title: Ganglioside mediate the interaction between Nogo receptor 1 and LINGO-1.
abstract: Upon spinal cord injury, the myelin inhibitors, including the myelin-associated glycoprotein (MAG), Nogo-A and the oligodendrocyte myelin glycoprotein (OMgp), bind to and signal via a single neuronal receptor/co-receptor complex comprising of Nogo receptor 1(NgR1)/LINGO-1 and p75 or TROY, impeding regeneration of injured axons. We employed a cell-free system to study the binding of NgR1 to its co-receptors and the myelin inhibitor Nogo-A, and show that gangliosides mediate the interaction of NgR1 with LINGO-1. Solid phase binding assays demonstrate that the sialic acid moieties of gangliosides and the stalk of NgR1 are the principal determinants of these molecular interactions. Moreover, the tripartite complex comprising of NgR1, LINGO-1 and ganglioside exhibits stronger binding to Nogo-A (Nogo-54) in the presence of p75, suggesting the gangliosides modulate the myelin inhibitor-receptor signaling.
authors.affiliation: Structural Biology Program, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, NY 10021, USA. sahan@mskcc.org
authors.forename: Nayanendu
authors.initials: N
authors.lastname: Saha
authors.forename: Momchil V
authors.initials: MV
authors.lastname: Kolev
authors.forename: Mariya
authors.initials: M
authors.lastname: Semavina
authors.forename: Juha
authors.initials: J
authors.lastname: Himanen
authors.forename: Dimitar B
authors.initials: DB
authors.lastname: Nikolov
mesh_terms: D002474:Cell-Free System / Q000378:metabolism; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D017434:Protein Structure, Tertiary; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D058851:GPI-Linked Proteins; D005732:Gangliosides; C482293:LINGO1 protein, human; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface; D019158:N-Acetylneuraminic Acid