title: Myocilin is involved in NgR1/Lingo-1-mediated oligodendrocyte differentiation and myelination of the optic nerve.
abstract: Myocilin is a secreted glycoprotein that belongs to a family of olfactomedin domain-containing proteins. Although myocilin is detected in several ocular and nonocular tissues, the only reported human pathology related to mutations in the MYOCILIN gene is primary open-angle glaucoma. Functions of myocilin are poorly understood. Here we demonstrate that myocilin is a mediator of oligodendrocyte differentiation and is involved in the myelination of the optic nerve in mice. Myocilin is expressed and secreted by optic nerve astrocytes. Differentiation of optic nerve oligodendrocytes is delayed in Myocilin-null mice. Optic nerves of Myocilin-null mice contain reduced levels of several myelin-associated proteins including myelin basic protein, myelin proteolipid protein, and 2'3'-cyclic nucleotide 3'-phosphodiesterase compared with those of wild-type littermates. This leads to reduced myelin sheath thickness of optic nerve axons in Myocilin-null mice compared with wild-type littermates, and this difference is more pronounced at early postnatal stages compared with adult mice. Myocilin also affects differentiation of oligodendrocyte precursors in vitro. Its addition to primary cultures of differentiating oligodendrocyte precursors increases levels of tested markers of oligodendrocyte differentiation and stimulates elongation of oligodendrocyte processes. Myocilin stimulation of oligodendrocyte differentiation occurs through the NgR1/Lingo-1 receptor complex. Myocilin physically interacts with Lingo-1 and may be considered as a Lingo-1 ligand. Myocilin-induced elongation of oligodendrocyte processes may be mediated by activation of FYN and suppression of RhoA GTPase.
authors.affiliation: Retinal Ganglion Cell Biology Section, Laboratory of Retinal Cell and Molecular Biology and Histology Core, National Eye Institute, National Institutes of Health (NIH), Bethesda, Maryland 20892, and Neuro-Oncology Branch, National Cancer Institute, NIH, Bethesda, Maryland 20892.
authors.forename: Heung Sun
authors.initials: HS
authors.lastname: Kwon
authors.forename: Naoki
authors.initials: N
authors.lastname: Nakaya
authors.forename: Mones
authors.initials: M
authors.lastname: Abu-Asab
authors.forename: Hong Sug
authors.initials: HS
authors.lastname: Kim
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Tomarev
mesh_terms: D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000235:genetics; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000070816:Nogo Receptor 1; D009836:Oligodendroglia / Q000502:physiology* / Q000648:ultrastructure; D009900:Optic Nerve / Q000166:cytology*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000502:physiology; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D005136:Eye Proteins; D058851:GPI-Linked Proteins; D006023:Glycoproteins; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070816:Nogo Receptor 1; D011956:Receptors, Cell Surface; D000099179:Myocilin; C482293:LINGO1 protein, human; C486580:RTN4R protein, human
keywords: Lingo-1; astrocyte; differentiation; myelin; myocilin; oligodendrocyte
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