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Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth - Nature

  • ️He, Zhigang
  • ️Sun Jun 16 2002
  • Letter
  • Published: 16 June 2002

Nature volume 417, pages 941–944 (2002)Cite this article

Abstract

The inhibitory activity associated with myelin is a major obstacle for successful axon regeneration in the adult mammalian central nervous system (CNS)1,2. In addition to myelin-associated glycoprotein (MAG)3,4 and Nogo-A5,6,7, available evidence suggests the existence of additional inhibitors in CNS myelin8. We show here that a glycosylphosphatidylinositol (GPI)-anchored CNS myelin protein, oligodendrocyte-myelin glycoprotein (OMgp), is a potent inhibitor of neurite outgrowth in cultured neurons. Like Nogo-A, OMgp contributes significantly to the inhibitory activity associated with CNS myelin. To further elucidate the mechanisms that mediate this inhibitory activity of OMgp, we screened an expression library and identified the Nogo receptor (NgR)9 as a high-affinity OMgp-binding protein. Cleavage of NgR and other GPI-linked proteins from the cell surface renders axons of dorsal root ganglia insensitive to OMgp. Introduction of exogenous NgR confers OMgp responsiveness to otherwise insensitive neurons. Thus, OMgp is an important inhibitor of neurite outgrowth that acts through NgR and its associated receptor complex. Interfering with the OMgp/NgR pathway may allow lesioned axons to regenerate after injury in vivo.

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Acknowledgements

We thank A. Habib and J. Flanagan for providing the anti-OMgp antibodies and the AP-5 plasmid, and M. Greenberg, X. He, D. Lowenstein and M. Tessier-Lavigne for reading the manuscript. This study was supported by the Alfred Sloan Foundation, the Burroughs Wellcome Fund, the EJLB Foundation, the International Spinal Research Trust, the John Merck Fund, the Klingenstein Fund, the Whitehall Foundation, and the National Institutes of Health (NIH). K.C.W. is a recipient of a Howard Hughes Predoctoral Fellowship. V.K. is supported by an NIH predoctoral training grant.

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Authors and Affiliations

  1. Division of Neuroscience, Children's Hospital, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Kevin C. Wang, Vuk Koprivica, Jieun A. Kim, Rajeev Sivasankaran & Zhigang He

  2. Program in Neuroscience, Harvard Medical School, 320 Longwood Avenue, Boston, Massachusetts, 02115, USA

    Kevin C. Wang, Vuk Koprivica, Rachel L. Neve & Zhigang He

  3. Aventis Pharmaceuticals, Bridgewater, New Jersey, 08807, USA

    Yong Guo

  4. McLean Hospital, 115 Mill Street, Belmont, Massachusetts, 02478, USA

    Rachel L. Neve

Authors

  1. Kevin C. Wang

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  2. Vuk Koprivica

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  3. Jieun A. Kim

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  4. Rajeev Sivasankaran

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  5. Yong Guo

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  6. Rachel L. Neve

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Correspondence to Zhigang He.

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Wang, K., Koprivica, V., Kim, J. et al. Oligodendrocyte-myelin glycoprotein is a Nogo receptor ligand that inhibits neurite outgrowth. Nature 417, 941–944 (2002). https://doi.org/10.1038/nature00867

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  • Received: 03 April 2002

  • Accepted: 23 May 2002

  • Published: 16 June 2002

  • Issue Date: 27 June 2002

  • DOI: https://doi.org/10.1038/nature00867