title: Olfactomedin 1 interacts with the Nogo A receptor complex to regulate axon growth.
abstract: Olfm1, a secreted highly conserved glycoprotein, is detected in peripheral and central nervous tissues and participates in neural progenitor maintenance, cell death in brain, and optic nerve arborization. In this study, we identified Olfm1 as a molecule promoting axon growth through interaction with the Nogo A receptor (NgR1) complex. Olfm1 is coexpressed with NgR1 in dorsal root ganglia and retinal ganglion cells in embryonic and postnatal mice. Olfm1 specifically binds to NgR1, as judged by alkaline phosphatase assay and coimmunoprecipitation. The addition of Olfm1 inhibited the growth cone collapse of dorsal root ganglia neurons induced by myelin-associated inhibitors, indicating that Olfm1 attenuates the NgR1 receptor functions. Olfm1 caused the inhibition of NgR1 signaling by interfering with interaction between NgR1 and its coreceptors p75NTR or LINGO-1. In zebrafish, inhibition of optic nerve extension by olfm1 morpholino oligonucleotides was partially rescued by dominant negative ngr1 or lingo-1. These data introduce Olfm1 as a novel NgR1 ligand that may modulate the functions of the NgR1 complex in axonal growth.
authors.affiliation: Section of Molecular Mechanisms of Glaucoma, Laboratory of Retinal Cell and Molecular Biology, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-0606, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakaya
authors.forename: Afia
authors.initials: A
authors.lastname: Sultana
authors.forename: Hee-Sheung
authors.initials: HS
authors.lastname: Lee
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Tomarev
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D016326:Extracellular Matrix Proteins / Q000378:metabolism / Q000502:physiology*; D006023:Glycoproteins / Q000378:metabolism / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000096:biosynthesis; D020439:Growth Cones / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009185:Myelin Proteins / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000070798:Nogo Proteins; D009900:Optic Nerve / Q000166:cytology / Q000196:embryology; D009928:Organ Specificity; D016716:PC12 Cells; D011485:Protein Binding; D051381:Rats; D020800:Receptor, Nerve Growth Factor / Q000378:metabolism; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016326:Extracellular Matrix Proteins; D006023:Glycoproteins; D049452:Green Fluorescent Proteins; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D020800:Receptor, Nerve Growth Factor; D029961:Zebrafish Proteins; D020742:rhoA GTP-Binding Protein; C482293:LINGO1 protein, human; C000603199:RTN4 protein, human; C000603201:Rtn4 protein, mouse; C000603197:Rtn4 protein, rat; C000592544:Rtn4a protein, zebrafish; C485184:enhanced green fluorescent protein; C486337:neurog1 protein, zebrafish; C081451:olfactomedin