Nogo-A, -B, and -C are found on the cell surface and interact together in many different cell types.
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.
Dodd
Dana A
DA
Brain Research Institute, University of Zürich and Department of Biology, ETH Zürich, CH-8057 Zürich, Switzerland. dodd@hifo.unizh.ch
Niederoest
Barbara
B
Bloechlinger
Stefan
S
Dupuis
Luc
L
Loeffler
Jean-Philippe
JP
Schwab
Martin E
ME
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
D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat