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Originally published in Science Express on 27 June 2002
Science 16 August 2002:
Vol. 297. no. 5584, pp. 1190 - 1193
DOI: 10.1126/science.1073031
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Reports

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

Betty P. Liu, Alyson Fournier, Tadzia GrandPré, Stephen M. Strittmatter*

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.

Department of Neurology and Section of Neurobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
*   To whom correspondence should be addressed. E-mail: stephen.strittmatter{at}yale.edu

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   Abstract »    Full Text »    PDF »
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