title: LOTUS suppresses axon growth inhibition by blocking interaction between Nogo receptor-1 and all four types of its ligand.
abstract: Axon growth inhibitors such as Nogo proteins, myelin-associated glycoprotein (MAG), oligodendrocyte myelin glycoprotein (OMgp), and B lymphocyte stimulator (BLyS) commonly bind to Nogo receptor-1 (NgR1), leading to enormous restriction of functional recovery after damage to the adult central nervous system. Recently, we found that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated Nogo signaling. However, whether LOTUS exerts antagonism of NgR1 when bound by the other three ligands has not been determined. Overexpression of LOTUS together with NgR1 in COS7 cells blocked the binding of MAG, OMgp, and BLyS to NgR1. In cultured dorsal root ganglion neurons in which endogenous LOTUS is only weakly expressed, overexpression of LOTUS suppressed growth cone collapse and neurite outgrowth inhibition induced by these three NgR1 ligands. LOTUS suppressed NgR1 ligand-induced growth cone collapse in cultured olfactory bulb neurons, which endogenously express LOTUS. Growth cone collapse was induced by NgR1 ligands in lotus-deficient mice. These data suggest that LOTUS functions as a potent endogenous antagonist for NgR1 when bound by all four known NgR1 ligands, raising the possibility that LOTUS may protect neurons from NgR1-mediated axonal growth inhibition and thereby may be useful for promoting neuronal regeneration as a potent inhibitor of NgR1.
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Suehiro-cho 1-7-29, Tsurumi-ward, Yokohama 230-0045, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kurihara
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Suehiro-cho 1-7-29, Tsurumi-ward, Yokohama 230-0045, Japan.
authors.forename: Masumi
authors.initials: M
authors.lastname: Iketani
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Ito
authors.affiliation: Division of Medical Life Science, Yokohama City University School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan; Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan.
authors.forename: Kuniyuki
authors.initials: K
authors.lastname: Nishiyama
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sakakibara
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan; Advanced Medical Research Center, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: Molecular Medical Bioscience Laboratory, Department of Medical Life Science, Yokohama City University Graduate School of Medical Life Science, Suehiro-cho 1-7-29, Tsurumi-ward, Yokohama 230-0045, Japan; Division of Medical Life Science, Yokohama City University School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan; Advanced Medical Research Center, Yokohama City University Graduate School of Medicine, Fukuura 3-9, Kanazawa-ward, Yokohama 236-0004, Japan. Electronic address: kohtaro@med.yokohama-cu.ac.jp.
authors.forename: Kohtaro
authors.initials: K
authors.lastname: Takei
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D053264:B-Cell Activating Factor / Q000378:metabolism; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics*; D020439:Growth Cones / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D018992:Myelin-Associated Glycoprotein / Q000378:metabolism; D009474:Neurons / Q000166:cytology*; D000070798:Nogo Proteins; D063345:Oligodendrocyte-Myelin Glycoprotein / Q000378:metabolism; D011485:Protein Binding / Q000235:genetics; D014162:Transfection
chemical_list: D053264:B-Cell Activating Factor; D002135:Calcium-Binding Proteins; C560339:Crtac1 protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D000070798:Nogo Proteins; D063345:Oligodendrocyte-Myelin Glycoprotein; C000603201:Rtn4 protein, mouse
keywords: Axon growth inhibitors; LOTUS; Neuronal regeneration; Nogo receptor-1 antagonist