title: Nogo-A, -B, and -C are found on the cell surface and interact together in many different cell types.
abstract: Nogo-A, -B, and -C are generated from the Nogo/RTN-4 gene and share a highly conserved C-terminal domain. They lack an N-terminal signal sequence and are predominantly localized to the endoplasmic reticulum (ER). We found the N terminus of endogenous Nogo-A exposed on the surface of fibroblasts, DRG neurons, and myoblasts. Surface-expressed Nogo-A was also present on presynaptic terminals of the neuromuscular junction and on DRG neurons in vivo. Surface biotinylations confirmed the presence of all Nogo isoforms on the surface. To search for proteins that interact with Nogo-A and suggest a function for the large intracellular pool of Nogo-A, immunoprecipitations were performed. Surprisingly, the most predominant proteins that interact with Nogo-A are Nogo-B and Nogo-C as seen with radiolabeled lysates and as confirmed by Western blotting in multiple cell lines. Nogo-A, -B, and -C share a 180-amino acid C-terminal domain with two highly conserved hydrophobic stretches that could form a channel or transporter in the ER and/or on the cell surface.
authors.affiliation: Brain Research Institute, University of Zürich and Department of Biology, ETH Zürich, CH-8057 Zürich, Switzerland. dodd@hifo.unizh.ch
authors.forename: Dana A
authors.initials: DA
authors.lastname: Dodd
authors.forename: Barbara
authors.initials: B
authors.lastname: Niederoest
authors.forename: Stefan
authors.initials: S
authors.lastname: Bloechlinger
authors.forename: Luc
authors.initials: L
authors.lastname: Dupuis
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Loeffler
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
mesh_terms: D016475:3T3 Cells; D000818:Animals; D019921:Biotinylation; D015153:Blotting, Western; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002850:Chromatography, Gel; D006224:Cricetinae; D005347:Fibroblasts / Q000378:metabolism; D005727:Ganglia, Spinal / Q000378:metabolism; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D051379:Mice; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000502:physiology*; D032446:Myoblasts / Q000378:metabolism; D041681:NIH 3T3 Cells; D009474:Neurons / Q000378:metabolism; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000378:metabolism; D016716:PC12 Cells; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D051381:Rats; D014162:Transfection
chemical_list: D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat