Myelin-Associated Glycoprotein as a Functional Ligand for the Nogo-66 Receptor
Abstract
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.
- Publication:
-
Science
- Pub Date:
- August 2002
- DOI:
- 10.1126/science.1073031
- Bibcode:
- 2002Sci...297.1190L
- Keywords:
-
- NEUROSCIENCE