Identification of a receptor mediating Nogo-66 inhibition of axonal regeneration

Nogo has been identified as a component of the central nervous system (CNS) myelin that prevents axonal regeneration in the adult vertebrate CNS. Analysis of Nogo-A has shown that an axon-inhibiting domain of 66 amino acids is expressed at the extracellular surface and at the endoplasmic reticulum l...

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Bibliographic Details
Published in:Nature (London) 2001-01, Vol.409 (6818), p.341-346
Main Authors: Strittmatter, Stephen M, Fournier, Alyson E, GrandPre, Tadzia
Format: Article
Language:English
Subjects:
3T3 Cells
Amino Acid Sequence
Amino acids
Animals
Axons - physiology
Binding Sites
Biochemistry
Biological and medical sciences
Cell Division
Cell Line
Cell receptors
Cell structures and functions
Cellular biology
Chickens
Cloning, Molecular
COS Cells
DNA, Complementary
Fundamental and applied biological sciences. Psychology
Gene Expression
GPI-Linked Proteins
Growth Cones
Humans
Mice
Miscellaneous
Molecular and cellular biology
Molecular Sequence Data
Myelin Proteins - chemistry
Myelin Proteins - physiology
Nerve Regeneration
Nervous system
Nogo protein
Nogo Proteins
Nogo Receptor 1
Protein Structure, Tertiary
Receptors, Cell Surface - genetics
Receptors, Cell Surface - metabolism
Recombinant Fusion Proteins - genetics
Recombinant Fusion Proteins - metabolism
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Summary:Nogo has been identified as a component of the central nervous system (CNS) myelin that prevents axonal regeneration in the adult vertebrate CNS. Analysis of Nogo-A has shown that an axon-inhibiting domain of 66 amino acids is expressed at the extracellular surface and at the endoplasmic reticulum lumen of transfected cells and oligodendrocytes. The acidic amino terminus of Nogo-A is detected at the cytosolic face of cellular membranes and may contribute to inhibition of axon regeneration at sites of oligodendrocyte injury. Here we show that the extracellular domain of Nogo (Nogo-66) inhibits axonal extension, but does not alter non-neuronal cell morphology. In contrast, a multivalent form of the N terminus of Nogo-A affects the morphology of both neurons and other cell types. Here we identify a brain-specific, leucine-rich-repeat protein with high affinity for soluble Nogo-66. Cleavage of the Nogo-66 receptor and other glycophosphatidylinositol-linked proteins from axonal surfaces renders neurons insensitive to Nogo-66. Nogo-66 receptor expression is sufficient to impart Nogo-66 axonal inhibition to unresponsive neurons. Disruption of the interaction between Nogo-66 and its receptor provides the potential for enhanced recovery after human CNS injury.
ISSN:0028-0836
1476-4687
DOI:10.1038/35053072