Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor

• Published in: Science (American Association for the Advancement of Science) 2002-08, Vol.297 (5584), p.1190-1193
• Main Authors: Liu, Betty P., Fournier, Alyson, GrandPré, Tadzia, Strittmatter, Stephen M.
• Format: Article
• Language: English
• Subjects: Anatomy; Animals; Axons; Axons - physiology; Binding Sites; Biological and medical sciences; Central nervous system; Chick Embryo; Cloning, Molecular; Composition; COS Cells; Development. Senescence. Regeneration. Transplantation; Environmental Influences; Fundamental and applied biological sciences. Psychology; Ganglia, Spinal - cytology; Ganglia, Spinal - embryology; Ganglia, Spinal - metabolism; Gangliosides; Gene Library; Glycoproteins; GPI-Linked Proteins; Growth cones; Inhibition; Injuries; Ligands; Mice; Myelin; Myelin Proteins - chemistry; Myelin Proteins - metabolism; Myelin Proteins - pharmacology; Myelin-Associated Glycoprotein - chemistry; Myelin-Associated Glycoprotein - genetics; Myelin-Associated Glycoprotein - metabolism; Nerve Regeneration; Nervous system; Neurites; Neurites - physiology; Neurons; Neurons - metabolism; Nogo Proteins; Nogo Receptor 1; Peptide Fragments - metabolism; Peptide Fragments - pharmacology; Phosphatidylinositol Diacylglycerol-Lyase; Protein structure; Protein Structure, Tertiary; Proteins; Receptors; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Recombinant Fusion Proteins - chemistry; Recombinant Fusion Proteins - metabolism; Sialic Acids - metabolism; Structure; Transfection; Type C Phospholipases - metabolism; Vertebrates: nervous system and sense organs
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1073031

Axonal regeneration in the adult central nervous system (CNS) is limited by two proteins in myelin, Nogo and myelin-associated glycoprotein (MAC). 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.