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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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Gradual loss of myelin and formation of an astrocytic scar during Wallerian degeneration in the human spinal cord.
A. Buss, G. A. Brook, B. Kakulas, D. Martin, R. Franzen, J. Schoenen, J. Noth, and A. B. Schmitt (2004)
Brain 127, 34-44
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Neurotrophins Elevate cAMP to Reach a Threshold Required to Overcome Inhibition by MAG through Extracellular Signal-Regulated Kinase-Dependent Inhibition of Phosphodiesterase.
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J. Neurosci. 23, 11770-11777
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Sialoside Specificity of the Siglec Family Assessed Using Novel Multivalent Probes: IDENTIFICATION OF POTENT INHIBITORS OF MYELIN-ASSOCIATED GLYCOPROTEIN.
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J. Biol. Chem. 278, 31007-31019
   Abstract »    Full Text »    PDF »
Nogo-A Inhibits Neurite Outgrowth and Cell Spreading with Three Discrete Regions.
T. Oertle, M. E. van der Haar, C. E. Bandtlow, A. Robeva, P. Burfeind, A. Buss, A. B. Huber, M. Simonen, L. Schnell, C. Brosamle, et al. (2003)
J. Neurosci. 23, 5393-5406
   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
Delayed Systemic Nogo-66 Receptor Antagonist Promotes Recovery from Spinal Cord Injury.
S. Li and S. M. Strittmatter (2003)
J. Neurosci. 23, 4219-4227
   Abstract »    Full Text »    PDF »
Macrophage-Derived Factors Stimulate Optic Nerve Regeneration.
Y. Yin, Q. Cui, Y. Li, N. Irwin, D. Fischer, A. R. Harvey, and L. I. Benowitz (2003)
J. Neurosci. 23, 2284-2293
   Abstract »    Full Text »    PDF »
Rho Kinase Inhibition Enhances Axonal Regeneration in the Injured CNS.
A. E. Fournier, B. T. Takizawa, and S. M. Strittmatter (2003)
J. Neurosci. 23, 1416-1423
   Abstract »    Full Text »    PDF »
Nogo-A and Myelin-Associated Glycoprotein Mediate Neurite Growth Inhibition by Antagonistic Regulation of RhoA and Rac1.
B. Niederost, T. Oertle, J. Fritsche, R. A. McKinney, and C. E. Bandtlow (2002)
J. Neurosci. 22, 10368-10376
   Abstract »    Full Text »    PDF »


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