title: Identification of the neogenin-binding site on the repulsive guidance molecule A.
abstract: Repulsive guidance molecule (RGM) is a membrane-bound protein that was originally identified as an axon guidance molecule in the chick retinotectal system. RGMa, one of the 3 isoforms found in mammals, is involved in laminar patterning, cephalic neural tube closure, axon guidance, and inhibition of axonal regeneration. In addition to its roles in the nervous system, RGMa plays a role in enhancing helper T-cell activation. Binding of RGM to its receptor, neogenin, is considered necessary to transduce these signals; however, information on the binding of RGM to neogenin is limited. Using co-immunoprecipitation studies, we have identified that the RGMa region required for binding to neogenin contains amino acids (aa) 259-295. Synthesized peptide consisting of aa 284-293 directly binds to the extracellular domain (ECD) of recombinant neogenin, and addition of this peptide inhibits RGMa-induced growth cone collapse in mouse cortical neurons. Thus, we propose that this peptide is a promising lead in finding reagents capable of inhibiting RGMa signaling.
authors.affiliation: Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
authors.forename: Takahide
authors.initials: T
authors.lastname: Itokazu
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujita
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Toshihide
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D000818:Animals; D001665:Binding Sites; D002540:Cerebral Cortex / Q000196:embryology; D018076:DNA, Complementary / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D058851:GPI-Linked Proteins / Q000737:chemistry / Q000378:metabolism; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D018076:DNA, Complementary; D058851:GPI-Linked Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010455:Peptides; D020033:Protein Isoforms; C522183:RGMA protein, human; C483496:Rgma protein, mouse; C091279:neogenin; D014841:von Willebrand Factor