title: A multi-domain fragment of Nogo-A protein is a potent inhibitor of cortical axon regeneration via Nogo receptor 1.
abstract: Nogo-A limits axon regeneration and functional recovery after central nervous system injury in adult mammals. Three regions of Nogo-A (Nogo-A-24, Nogo-66, and Nogo-C39) interact with the neuronal Nogo-66 receptor 1 (NgR1). Nogo-66 also interacts with a structurally unrelated cell surface receptor, paired immunoglobulin-like receptor (PirB). We show here that the other two NgR1-interacting domains, Nogo-A-24 and Nogo-C39, also bind to PirB with high affinity. A purified 22-kDa protein containing all three NgR1- and PirB-interacting domains (Nogo-22) is a substantially more potent growth cone-collapsing molecule than Nogo-66 for chick dorsal root ganglion neurons and mature cortical neurons. Moreover, Nogo-22 inhibits axon regeneration of mature cortical neurons in vitro more potently than does Nogo-66. Although all three NgR1-interacting domains of Nogo-A also interact with PirB, expression of PirB in mature cortical cultures is nearly undetectable. Consistent with a relatively minor role for PirB in mature cortical neurons, Nogo-22 inhibition of axon regeneration is abolished by genetic deletion of NgR1. Thus, NgR1 is the predominant receptor for Nogo-22 in regenerating cortical neurons.
authors: Department of Neurology and Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, Connecticut 06536, USA.
authors: Eric A
authors: EA
authors: Huebner
authors: Byung G
authors: BG
authors: Kim
authors: Philip J
authors: PJ
authors: Duffy
authors: Rebecca H
authors: RH
authors: Brown
authors: Stephen M
authors: SM
authors: Strittmatter
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D002645:Chickens; D002522:Chlorocebus aethiops; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000378:metabolism; D006801:Humans; D051379:Mice; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*
chemical_list: D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; C105949:Pirb protein, mouse; C000603199:RTN4 protein, human; C486580:RTN4R protein, human; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C000603201:Rtn4 protein, mouse