Nogo and the Nogo-66 receptor.
Nogo has been identified as a component of central nervous system (CNS) myelin preventing axonal regeneration in the adult vertebrate CNS. Our previous analysis of Nogo-A demonstrated that an axon-inhibiting 66 aa domain is expressed at the extracellular surface and the endoplasmic reticulum lumen of transfected cells and oligodendrocytes. We have identified a brain-specific, leucine-rich repeat protein with high affinity for soluble Nogo-66. Cleavage of the Nogo-66 receptor from axonal surfaces renders neurons insensitive to Nogo-66. Nogo-66 receptor expression is sufficient to impart Nogo-66 axonal inhibition to unresponsive neurons. With identified ligand and receptor components, structure-function determinants for inhibition of axon regeneration can now be mapped. The relative contribution of Nogo, myelin-associated glycoprotein, chondroitin sulfate proteoglycan and oligodendrocyte myelin glycoprotein to myelin inhibition can be assessed. Blockade of Nogo-66 interaction with its receptor provides one potential avenue to promote axonal regeneration after adult mammalian CNS injury.
Fournier
Alyson E
AE
Department of Neurology, Section of Neurobiology, Yale University School of Medicine, P.O. Box 208018, New Haven, CT 06510, USA.
GrandPré
Tadzia
T
Gould
Graham
G
Wang
Xingxing
X
Strittmatter
Stephen M
SM
D000818:Animals; D001369:Axons / Q000502:physiology; D058851:GPI-Linked Proteins; D006131:Growth Inhibitors / Q000502:physiology*; D006801:Humans; D009185:Myelin Proteins / Q000502:physiology*; D009186:Myelin Sheath / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction
D058851:GPI-Linked Proteins; D006131:Growth Inhibitors; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface