Redundant Pathways Against Neuronal Regeneration

Science's STKE  20 Aug 2002:
Vol. 2002, Issue 146, pp. tw311
DOI: 10.1126/stke.2002.146.tw311

In vertebrates, severed nerves in the limbs can regrow and re-innervate their targets, restoring movement and sensory input. Similar injuries to the brain or spinal cord are not repaired, however, because of two inhibitory molecules in the myelin sheaths of central nerves that prevent neural regeneration--Nogo and myelin-associated glycoprotein (MAG). The glycosylphosphatidylinositol-linked receptor for Nogo has no intracellular domain, but the receptor for MAG is not definitively known, although it does bind sialic acid. In a screen designed to find other membrane proteins that might mediate the transmembrane signal of the Nogo receptor, Liu et al. (see the Perspective by Woolf and Bloechlinger) identified MAG as a primary ligand. This binding is of an appropriately high affinity to control the growth cone-collapsing effects of MAG and to ensure that expression of the Nogo receptor confers MAG sensitivity to embryonic neurons. Thus, both MAG and Nogo activate the Nogo receptor and act as redundant signals to inhibit neural regeneration.

B. P. Liu, A. Fournier, T. GrandPré, S. M. Strittmatter, Myelin-associated glycoprotein as a functional ligand for the Nogo-66 receptor, Science 297, 1190-1193 (2002). [Abstract] [Full Text]

C. J. Woolf, S. Bloechlinger, It takes more than two to Nogo, Science 297, 1132-1134 (2002). [Summary] [Full Text]