Nogos and the Nogo-66 receptor: factors inhibiting CNS neuron regeneration.
The recently cloned gene Nogo, whose alternative splice products correspond to the antigenic target of the central nervous system (CNS) regeneration enhancing monoclonal antibody IN-1, codes for membrane proteins enriched in brain, particularly in oligodendrocytes. The 66-amino acid extracellular domain of Nogo (Nogo-66) interacts with a high-affinity receptor (NgR), a glycosylphosphatidylinositol (GPI)-linked protein with multiple leucine-rich repeats. The amino terminal cytoplasmic domain of Nogo appears to have a general cellular growth inhibitory effect. Nogo-66, on the other hand, specifically retards neurite outgrowth and induces growth cone collapse, possibly through its interaction with NgR and as yet unidentified transmembrane coreceptors. Recent results also suggest that Nogo expression may induce apoptosis in tumor cells. Together, these proteins provide new molecular handles for the design of therapeutic interventions for CNS injuries and neurodegenerative diseases, as well as possible leads to anticancer strategies.
Ng
Cherry Ee Lin
CE
NCA Lab, Institute of Molecular and Cell Biology, Singapore, Republic of Singapore.
Tang
Bor Luen
BL
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002490:Central Nervous System / Q000254:growth & development* / Q000378:metabolism*; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020439:Growth Cones / Q000378:metabolism*; D006801:Humans; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009416:Nerve Regeneration / Q000502:physiology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface