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Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein

Author

Listed:
  • Tadzia GrandPré

    (Department of Neurology)

  • Fumio Nakamura

    (Department of Neurology)

  • Timothy Vartanian

    (Beth Israel Deaconess Medical Center, Harvard Institutes of Medicine)

  • Stephen M. Strittmatter

    (Department of Neurology
    Section of Neurobiology, Yale University School of Medicine)

Abstract

Adult mammalian axon regeneration is generally successful in the peripheral nervous system (PNS) but is dismally poor in the central nervous system (CNS). However, many classes of CNS axons can extend for long distances in peripheral nerve grafts1. A comparison of myelin from the CNS and the PNS has revealed that CNS white matter is selectively inhibitory for axonal outgrowth2. Several components of CNS white matter, NI35, NI250(Nogo) and MAG, that have inhibitory activity for axon extension have been described3,4,5,6,7. The IN-1 antibody, which recognizes NI35 and NI250(Nogo), allows moderate degrees of axonal regeneration and functional recovery after spinal cord injury8,9. Here we identify Nogo as a member of the Reticulon family, Reticulon 4-A. Nogo is expressed by oligodendrocytes but not by Schwann cells, and associates primarily with the endoplasmic reticulum. A 66-residue lumenal/extracellular domain inhibits axonal extension and collapses dorsal root ganglion growth cones. In contrast to Nogo, Reticulon 1 and 3 are not expressed by oligodendrocytes, and the 66-residue lumenal/extracellular domains from Reticulon 1, 2 and 3 do not inhibit axonal regeneration. These data provide a molecular basis to assess the contribution of Nogo to the failure of axonal regeneration in the adult CNS.

Suggested Citation

  • Tadzia GrandPré & Fumio Nakamura & Timothy Vartanian & Stephen M. Strittmatter, 2000. "Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein," Nature, Nature, vol. 403(6768), pages 439-444, January.
    • Handle: RePEc:nat:nature:v:403:y:2000:i:6768:d:10.1038_35000226
    DOI: 10.1038/35000226
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    Cited by:

    1. Weiping Zhu & Han Zhang & Xuning Chen & Kan Jin & Le Ning, 2018. "Numerical characterization of regenerative axons growing along a spherical multifunctional scaffold after spinal cord injury," PLOS ONE, Public Library of Science, vol. 13(10), pages 1-22, October.
    2. Fereshteh Pourabdolhossein & Sabah Mozafari & Ghislaine Morvan-Dubois & Javad Mirnajafi-Zadeh & Alejandra Lopez-Juarez & Jacqueline Pierre-Simons & Barbara A Demeneix & Mohammad Javan, 2014. "Nogo Receptor Inhibition Enhances Functional Recovery following Lysolecithin-Induced Demyelination in Mouse Optic Chiasm," PLOS ONE, Public Library of Science, vol. 9(9), pages 1-13, September.
    3. Anthony G. Boghdadi & Joshua Spurrier & Leon Teo & Mingfeng Li & Mario Skarica & Benjamin Cao & William C. Kwan & Tobias D. Merson & Susan K. Nilsson & Nenad Sestan & Stephen M. Strittmatter & James A, 2021. "NogoA-expressing astrocytes limit peripheral macrophage infiltration after ischemic brain injury in primates," Nature Communications, Nature, vol. 12(1), pages 1-16, December.

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