Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Applied Biosystems

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Published Online June 27, 2002
Science DOI: 10.1126/science.1073031

Reports

Submitted on April 18, 2002
Accepted on June 13, 2002

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

Betty P. Liu 1, Alyson Fournier 1, Tadzia GrandPré 1, Stephen M. Strittmatter 1*

1 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.

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 GPI-anchored protein, while 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 limiting axonal regeneration after CNS injury.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Inactivation of Glycogen Synthase Kinase 3 Promotes Axonal Growth and Recovery in the CNS.
J. Dill, H. Wang, F. Zhou, and S. Li (2008)
J. Neurosci. 28, 8914-8928
   Abstract »    Full Text »    PDF »
Spinal Cord Repair: Bridging the Divide.
P. Verma, G. Garcia-Alias, and J. W. Fawcett (2008)
Neurorehabil Neural Repair 22, 429-437
   Abstract »    PDF »
Nogo-A and Myelin-Associated Glycoprotein Differently Regulate Oligodendrocyte Maturation and Myelin Formation.
V. Pernet, S. Joly, F. Christ, L. Dimou, and M. E. Schwab (2008)
J. Neurosci. 28, 7435-7444
   Abstract »    Full Text »    PDF »
Ganglioside Inhibition of Neurite Outgrowth Requires Nogo Receptor Function: IDENTIFICATION OF INTERACTION SITES AND DEVELOPMENT OF NOVEL ANTAGONISTS.
G. Williams, A. Wood, E.-J. Williams, Y. Gao, M. L. Mercado, A. Katz, D. Joseph-McCarthy, B. Bates, H.-P. Ling, A. Aulabaugh, et al. (2008)
J. Biol. Chem. 283, 16641-16652
   Abstract »    Full Text »    PDF »
Nogo-66 Receptor Antagonist Peptide (NEP1-40) Administration Promotes Functional Recovery and Axonal Growth After Lateral Funiculus Injury in the Adult Rat.
Y. Cao, J.S. Shumsky, M.A. Sabol, R.A. Kushner, S. Strittmatter, F.P.T. Hamers, D.H.S. Lee, S.A. Rabacchi, and M. Murray (2008)
Neurorehabil Neural Repair 22, 262-278
   Abstract »    PDF »
ROCK and Rho: Biochemistry and Neuronal Functions of Rho-Associated Protein Kinases.
A. Schmandke, A. Schmandke, and S. M. Strittmatter (2007)
Neuroscientist 13, 454-469
   Abstract »    PDF »
Gangliosides and Nogo Receptors Independently Mediate Myelin-associated Glycoprotein Inhibition of Neurite Outgrowth in Different Nerve Cells.
N. R. Mehta, P. H. H. Lopez, A. A. Vyas, and R. L. Schnaar (2007)
J. Biol. Chem. 282, 27875-27886
   Abstract »    Full Text »    PDF »
The Inhibition Site on Myelin-Associated Glycoprotein Is within Ig-Domain 5 and Is Distinct from the Sialic Acid Binding Site.
Z. Cao, J. Qiu, M. Domeniconi, J. Hou, J. B. Bryson, W. Mellado, and M. T. Filbin (2007)
J. Neurosci. 27, 9146-9154
   Abstract »    Full Text »    PDF »
ATF3 Increases the Intrinsic Growth State of DRG Neurons to Enhance Peripheral Nerve Regeneration.
R. Seijffers, C. D. Mills, and C. J. Woolf (2007)
J. Neurosci. 27, 7911-7920
   Abstract »    Full Text »    PDF »
The Nogo-66 Receptor NgR1 Is Required Only for the Acute Growth Cone-Collapsing But Not the Chronic Growth-Inhibitory Actions of Myelin Inhibitors.
O. Chivatakarn, S. Kaneko, Z. He, M. Tessier-Lavigne, and R. J. Giger (2007)
J. Neurosci. 27, 7117-7124
   Abstract »    Full Text »    PDF »
Molecular dissection of the myelin-associated glycoprotein receptor complex reveals cell type-specific mechanisms for neurite outgrowth inhibition.
K. Venkatesh, O. Chivatakarn, S.-S. Sheu, and R. J. Giger (2007)
J. Cell Biol. 177, 393-399
   Abstract »    Full Text »    PDF »
Elongation of Axons during Regeneration Involves Retinal Crystallin {beta} b2 (crybb2).
T. Liedtke, J. C. Schwamborn, U. Schroer, and S. Thanos (2007)
Mol. Cell. Proteomics 6, 895-907
   Abstract »    Full Text »    PDF »
Nonsteroidal Anti-Inflammatory Drugs Promote Axon Regeneration via RhoA Inhibition.
Q. Fu, J. Hue, and S. Li (2007)
J. Neurosci. 27, 4154-4164
   Abstract »    Full Text »    PDF »
Characterization of Myelin Ligand Complexes with Neuronal Nogo-66 Receptor Family Members.
J. Lauren, F. Hu, J. Chin, J. Liao, M. S. Airaksinen, and S. M. Strittmatter (2007)
J. Biol. Chem. 282, 5715-5725
   Abstract »    Full Text »    PDF »
Passive Immunization with Anti-Ganglioside Antibodies Directly Inhibits Axon Regeneration in an Animal Model.
H. C. Lehmann, P. H. H. Lopez, G. Zhang, T. Ngyuen, J. Zhang, B. C. Kieseier, S. Mori, and K. A. Sheikh (2007)
J. Neurosci. 27, 27-34
   Abstract »    Full Text »    PDF »
Subcutaneous Nogo Receptor Removes Brain Amyloid-{beta} and Improves Spatial Memory in Alzheimer's Transgenic Mice.
J. H. Park, G. A. Widi, D. A. Gimbel, N. Y. Harel, D. H. S. Lee, and S. M. Strittmatter (2006)
J. Neurosci. 26, 13279-13286
   Abstract »    Full Text »    PDF »
The Structure of the Lingo-1 Ectodomain, a Module Implicated in Central Nervous System Repair Inhibition.
L. Mosyak, A. Wood, B. Dwyer, M. Buddha, M. Johnson, A. Aulabaugh, X. Zhong, E. Presman, S. Benard, K. Kelleher, et al. (2006)
J. Biol. Chem. 281, 36378-36390
   Abstract »    Full Text »    PDF »
The Nogo-Nogo Receptor Pathway Limits a Spectrum of Adult CNS Axonal Growth..
W. B. J. Cafferty and S. M. Strittmatter (2006)
J. Neurosci. 26, 12242-12250
   Abstract »    Full Text »    PDF »
Sialidase enhances spinal axon outgrowth in vivo.
L. J. S. Yang, I. Lorenzini, K. Vajn, A. Mountney, L. P. Schramm, and R. L. Schnaar (2006)
PNAS 103, 11057-11062
   Abstract »    Full Text »    PDF »
Neurotrophins support regenerative axon assembly over CSPGs by an ECM-integrin-independent mechanism.
F.-Q. Zhou, M. Walzer, Y.-H. Wu, J. Zhou, S. Dedhar, and W. D. Snider (2006)
J. Cell Sci. 119, 2787-2796
   Abstract »    Full Text »    PDF »
Myelin-associated Glycoprotein Inhibits Microtubule Assembly by a Rho-kinase-dependent Mechanism.
F. Mimura, S. Yamagishi, N. Arimura, M. Fujitani, T. Kubo, K. Kaibuchi, and T. Yamashita (2006)
J. Biol. Chem. 281, 15970-15979
   Abstract »    Full Text »    PDF »
NG2 glial cells provide a favorable substrate for growing axons..
Z. Yang, R. Suzuki, S. B. Daniels, C. B. Brunquell, C. J. Sala, and A. Nishiyama (2006)
J. Neurosci. 26, 3829-3839
   Abstract »    Full Text »    PDF »
Neurotrophic factor synergy is required for neuronal survival and disinhibited axon regeneration after CNS injury.
A. Logan, Z. Ahmed, A. Baird, A. M. Gonzalez, and M. Berry (2006)
Brain 129, 490-502
   Abstract »    Full Text »    PDF »
Siglecs--the major subfamily of I-type lectins.
A. Varki and T. Angata (2006)
Glycobiology 16, 1R-27R
   Abstract »    Full Text »    PDF »
Ephrin-B3 is a myelin-based inhibitor of neurite outgrowth.
M. D. Benson, M. I. Romero, M. E. Lush, Q. R. Lu, M. Henkemeyer, and L. F. Parada (2005)
PNAS 102, 10694-10699
   Abstract »    Full Text »    PDF »
Nogo-A Interacts with the Nogo-66 Receptor through Multiple Sites to Create an Isoform-Selective Subnanomolar Agonist.
F. Hu, B. P. Liu, S. Budel, J. Liao, J. Chin, A. Fournier, and S. M. Strittmatter (2005)
J. Neurosci. 25, 5298-5304
   Abstract »    Full Text »    PDF »
Three's Company: Two or More Unrelated Receptors Pair with the Same Ligand.
I. Ben-Shlomo and A. J. W. Hsueh (2005)
Mol. Endocrinol. 19, 1097-1109
   Abstract »    Full Text »    PDF »
Potent Glycan Inhibitors of Myelin-associated Glycoprotein Enhance Axon Outgrowth in Vitro.
A. A. Vyas, O. Blixt, J. C. Paulson, and R. L. Schnaar (2005)
J. Biol. Chem. 280, 16305-16310
   Abstract »    Full Text »    PDF »
Overcoming the Inhibitors of Myelin with a Novel Neurotrophin Strategy.
G. Williams, E.-J. Williams, P. Maison, M. N. Pangalos, F. S. Walsh, and P. Doherty (2005)
J. Biol. Chem. 280, 5862-5869
   Abstract »    Full Text »    PDF »
Combining Schwann Cell Bridges and Olfactory-Ensheathing Glia Grafts with Chondroitinase Promotes Locomotor Recovery after Complete Transection of the Spinal Cord.
K. Fouad, L. Schnell, M. B. Bunge, M. E. Schwab, T. Liebscher, and D. D. Pearse (2005)
J. Neurosci. 25, 1169-1178
   Abstract »    Full Text »    PDF »
Sequential loss of myelin proteins during Wallerian degeneration in the human spinal cord.
A. Buss, K. Pech, D. Merkler, B. A. Kakulas, D. Martin, J. Schoenen, J. Noth, M. E. Schwab, and G. A. Brook (2005)
Brain 128, 356-364
   Abstract »    Full Text »    PDF »
The Nogo-66 Receptor Homolog NgR2 Is a Sialic Acid-Dependent Receptor Selective for Myelin-Associated Glycoprotein.
K. Venkatesh, O. Chivatakarn, H. Lee, P. S. Joshi, D. B. Kantor, B. A. Newman, R. Mage, C. Rader, and R. J. Giger (2005)
J. Neurosci. 25, 808-822
   Abstract »    Full Text »    PDF »
The role of the Rho GTPases in neuronal development.
E.-E. Govek, S. E. Newey, and L. Van Aelst (2005)
Genes & Dev. 19, 1-49
   Abstract »    Full Text »    PDF »
Rho-Kinase Inhibition Enhances Axonal Plasticity and Attenuates Cold Hyperalgesia after Dorsal Rhizotomy.
L. M. Ramer, J. F. Borisoff, and M. S. Ramer (2004)
J. Neurosci. 24, 10796-10805
   Abstract »    Full Text »    PDF »
Immunity to the Extracellular Domain of Nogo-A Modulates Experimental Autoimmune Encephalomyelitis.
P. Fontoura, P. P. Ho, J. DeVoss, B. Zheng, B. J. Lee, B. A. Kidd, H. Garren, R. A. Sobel, W. H. Robinson, M. Tessier-Lavigne, et al. (2004)
J. Immunol. 173, 6981-6992
   Abstract »    Full Text »    PDF »
Blockade of Nogo-66, Myelin-Associated Glycoprotein, and Oligodendrocyte Myelin Glycoprotein by Soluble Nogo-66 Receptor Promotes Axonal Sprouting and Recovery after Spinal Injury.
S. Li, B. P. Liu, S. Budel, M. Li, B. Ji, L. Walus, W. Li, A. Jirik, S. Rabacchi, E. Choi, et al. (2004)
J. Neurosci. 24, 10511-10520
   Abstract »    Full Text »    PDF »
Axonal Regeneration and Lack of Astrocytic Gliosis in EphA4-Deficient Mice.
Y. Goldshmit, M. P. Galea, G. Wise, P. F. Bartlett, and A. M. Turnley (2004)
J. Neurosci. 24, 10064-10073
   Abstract »    Full Text »    PDF »
A Neutralizing Anti-Nogo66 Receptor Monoclonal Antibody Reverses Inhibition of Neurite Outgrowth by Central Nervous System Myelin.
W. Li, L. Walus, S. A. Rabacchi, A. Jirik, E. Chang, J. Schauer, B. H. Zheng, N. J. Benedetti, B. P. Liu, E. Choi, et al. (2004)
J. Biol. Chem. 279, 43780-43788
   Abstract »    Full Text »    PDF »
Nogo Receptor Antagonism Promotes Stroke Recovery by Enhancing Axonal Plasticity.
J.-K. Lee, J.-E. Kim, M. Sivula, and S. M. Strittmatter (2004)
J. Neurosci. 24, 6209-6217
   Abstract »    Full Text »    PDF »
The phosphodiesterase inhibitor rolipram delivered after a spinal cord lesion promotes axonal regeneration and functional recovery.
E. Nikulina, J. L. Tidwell, H. N. Dai, B. S. Bregman, and M. T. Filbin (2004)
PNAS 101, 8786-8790
   Abstract »    Full Text »    PDF »
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
   Abstract »    Full Text »    PDF »
Identification of Nogo-66 Receptor (NgR) and Homologous Genes in Fish.
M. Klinger, J. S. Taylor, T. Oertle, M. E. Schwab, C. A. O. Stuermer, and H. Diekmann (2004)
Mol. Biol. Evol. 21, 76-85
   Abstract »    Full Text »    PDF »
Neurotrophins Elevate cAMP to Reach a Threshold Required to Overcome Inhibition by MAG through Extracellular Signal-Regulated Kinase-Dependent Inhibition of Phosphodiesterase.
Y. Gao, E. Nikulina, W. Mellado, and M. T. Filbin (2003)
J. Neurosci. 23, 11770-11777
   Abstract »    Full Text »    PDF »
Sialoside Specificity of the Siglec Family Assessed Using Novel Multivalent Probes: IDENTIFICATION OF POTENT INHIBITORS OF MYELIN-ASSOCIATED GLYCOPROTEIN.
O. Blixt, B. E. Collins, I. M. van den Nieuwenhof, P. R. Crocker, and J. C. Paulson (2003)
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 »
A reticular rhapsody: phylogenic evolution and nomenclature of the RTN/Nogo gene family.
T. OERTLE, M. KLINGER, C. A. O. STUERMER, and M. E. SCHWAB (2003)
FASEB J 17, 1238-1247
   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 »


ADVERTISEMENT
Click Me!

ADVERTISEMENT
Click Me!

To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)