Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact.
Axon regeneration in the adult CNS is limited by the presence of inhibitory proteins. An interaction of Nogo on the oligodendrocyte surface with Nogo-66 Receptor (NgR) on axons has been suggested to play an important role in limiting axonal growth. Here, we compare the localization of these two proteins immunohistochemically as a test of this hypothesis. Throughout much of the adult CNS, Nogo-A is detected on oligodendrocyte processes surrounding myelinated axons, including areas of axon-oligodendrocyte contact. The NgR protein is detected selectively in neurons and is present throughout axons, indicating that Nogo-A and its receptor are juxtaposed along the course of myelinated fibers. NgR protein expression is restricted to postnatal neurons and their axons. In contrast, Nogo-A is observed in myelinating oligodendrocytes, embryonic muscle, and neurons, suggesting that Nogo-A has additional physiologic roles unrelated to NgR binding. After spinal cord injury, Nogo-A is upregulated to a moderate degree, whereas NgR levels are maintained at constant levels. Taken together, these data confirm the apposition of Nogo ligand and NgR receptor in situations of limited axonal regeneration and support the hypothesis that this system regulates CNS axonal plasticity and recovery from injury.
Wang
Xingxing
X
Departments of Neurology and Neurosurgery and Section of Neurobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Chun
Soo-Jin
SJ
Treloar
Helen
H
Vartanian
Timothy
T
Greer
Charles A
CA
Strittmatter
Stephen M
SM
D000818:Animals; D001369:Axons / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure; D001921:Brain / Q000196:embryology / Q000254:growth & development; D001923:Brain Chemistry; D058851:GPI-Linked Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins / Q000032:analysis*; D009186:Myelin Sheath / Q000737:chemistry*; D009416:Nerve Regeneration; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D009836:Oligodendroglia / Q000737:chemistry; D011956:Receptors, Cell Surface / Q000032:analysis*; D013116:Spinal Cord / Q000737:chemistry / Q000601:surgery; D013569:Synapses / Q000737:chemistry*; D014018:Tissue Distribution
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; C000603201:Rtn4 protein, mouse; C419790:Rtn4r protein, mouse