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

Science  16 Aug 2002:
Vol. 297, Issue 5584, pp. 1190-1193
DOI: 10.1126/science.1073031

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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.

  • * To whom correspondence should be addressed. E-mail: stephen.strittmatter{at}yale.edu

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