Nogo-A is a myelin-associated neurite outgrowth inhibitor and an antigen for monoclonal antibody IN-1.
The capacity of the adult brain and spinal cord to repair lesions by axonal regeneration or compensatory fibre growth is extremely limited. A monoclonal antibody (IN-1) raised against NI-220/250, a myelin protein that is a potent inhibitor of neurite growth, promoted axonal regeneration and compensatory plasticity following lesions of the central nervous system (CNS) in adult rats. Here we report the cloning of nogo A, the rat complementary DNA encoding NI-220/250. The nogo gene encodes at least three major protein products (Nogo-A, -B and -C). Recombinant Nogo-A is recognized by monoclonal antibody IN-1, and it inhibits neurite outgrowth from dorsal root ganglia and spreading of 3T3 fibroblasts in an IN-1-sensitive manner. Antibodies against Nogo-A stain CNS myelin and oligodendrocytes and allow dorsal root ganglion neurites to grow on CNS myelin and into optic nerve explants. These data show that Nogo-A is a potent inhibitor of neurite growth and an IN-1 antigen produced by oligodendrocytes, and may allow the generation of new reagents to enhance CNS regeneration and plasticity.
Chen
M S
MS
Brain Research Institute, Department of Neuromorphology, University of Zurich, Switzerland.
Huber
A B
AB
van der Haar
M E
ME
Frank
M
M
Schnell
L
L
Spillmann
A A
AA
Christ
F
F
Schwab
M E
ME
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D016466:CHO Cells; D002417:Cattle; D002478:Cells, Cultured; D003001:Cloning, Molecular; D006224:Cricetinae; D018076:DNA, Complementary; D006031:Glycosylation; D006131:Growth Inhibitors / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D009185:Myelin Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D009416:Nerve Regeneration; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D000070798:Nogo Proteins; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000502:physiology; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D014018:Tissue Distribution
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D006131:Growth Inhibitors; D008565:Membrane Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D020033:Protein Isoforms; C000603199:RTN4 protein, human; D011994:Recombinant Proteins; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat