Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor.
Axonal regeneration in the adult central nervous system (CNS) is limited by two proteins in myelin, Nogo and myelin-associated glycoprotein (MAG). The receptor for Nogo (NgR) has been identified as an axonal glycosyl-phosphatidyl-inositol (GPI)-anchored protein, whereas the MAG receptor has remained elusive. Here, we show that MAG binds directly, with high affinity, to NgR. Cleavage of GPI-linked proteins from axons protects growth cones from MAG-induced collapse, and dominant-negative NgR eliminates MAG inhibition of neurite outgrowth. MAG-resistant embryonic neurons are rendered MAG-sensitive by expression of NgR. MAG and Nogo-66 activate NgR independently and serve as redundant NgR ligands that may limit axonal regeneration after CNS injury.
Liu
Betty P
BP
Department of Neurology and Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Fournier
Alyson
A
GrandPré
Tadzia
T
Strittmatter
Stephen M
SM
D000818:Animals; D001369:Axons / Q000502:physiology*; D001665:Binding Sites; D019556:COS Cells; D002642:Chick Embryo; D003001:Cloning, Molecular; D058851:GPI-Linked Proteins; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D015723:Gene Library; D008024:Ligands; D051379:Mice; D009185:Myelin Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D018992:Myelin-Associated Glycoprotein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D058851:GPI-Linked Proteins; D008024:Ligands; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; C499213:NEPI-40 protein, mouse; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C419790:Rtn4r protein, mouse; C486581:Rtn4r protein, rat; D012794:Sialic Acids; D010738:Type C Phospholipases; D043265:Phosphatidylinositol Diacylglycerol-Lyase