Editors' ChoiceNeurobiology

An Inhibitor of Nerve Regrowth Revealed

Science's STKE  01 Feb 2000:
Vol. 2000, Issue 17, pp. tw5
DOI: 10.1126/stke.2000.17.tw5

Three groups report the cloning and characterization of a myelin protein, Nogo, which inhibits the outgrowth of central nervous system neurons. Goldberg and Barres highlight these reports in a Nature news and views article. Nogo belongs to the Reticulon family of proteins, which have two putative transmembrane domains and a COOH-terminal endoplasmic reticulum retention signal. All three groups identified three transcripts with Nogo-A being the longest and Nogo-B and Nogo-C encoding variants with smaller NH2-terminal domains. Chen et al. identified rat Nogos and demonstrated that Nogo-A was restricted in expression to nervous tissue. Prinjha et al. and GrandPré et al. both identified human Nogos. Each group used different approaches to identify the regions responsible for inhibiting neurite outgrowth and reported different regions of Nogo-A as having the inhibitory activity. All of the regions identified would not be displayed extracellularly if Nogo-A had only the two predicted transmembrane domains raising the issue of the topology of Nogo proteins. Nogo-A was found to be predominantly intracellular raising the question of how Nogo proteins act as myelin-associated inhibitors of nerve regeneration.

Chen, M.S., Huber, A.B., van der Haar, M.E., Frank, M., Schnell, L., Spillmann, A.A., Christ, F., and Schwab, M.E. (2000) Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for the monoclonal IN-1. Nature 403: 434-438. [Online Journal]

Prinjha, R., Moore, S.E., Vinson, M., Blake, S., Morrow, R., Christie, G., Michalovish, D., Simmons, D.L., and Walsh, F.S. (2000) Inhibitor of neurite outgrowth in humans. Nature 403: 383-384. [Online Journal]

GrandPré, T., Nakamura, F., Vartanian, T., and Strittmatter, S.M. (2000) Identification of the Nogo inhibitor of axon regeneration as a Reticulon protein. Nature 403: 439-444. [Online Journal]

Goldberg, J.L. and Barres, B.A. (2000) Nogo in nerve regeneration. Nature 403: 369-370. [Online Journal]