title: Optimedin: a novel olfactomedin-related protein that interacts with myocilin.
abstract: Mutations in the MYOC gene may lead to juvenile open-angle glaucoma with high intraocular pressure, and are detected in about 4% of people with adult onset glaucoma. Most of these mutations are found in the third exon of the gene encoding the olfactomedin-like domain located at the C terminus of the protein. Another olfactomedin-related protein, known as noelin or pancortin, is involved in the generation of neural crest cells. Here we describe the identification of a novel olfactomedin-related gene, named optimedin, located on chromosome 1p21 in humans. Optimedin and noelin are both expressed in brain and retina. However, unlike noelin, rat optimedin is also highly expressed in the epithelial cells of the iris and the ciliary body in close proximity to the sites of Myoc expression. In the human eye, optimedin is expressed in the retina and the trabecular meshwork. Both optimedin and myocilin are localized in Golgi and are secreted proteins. The presence of mutant myocilin interferes with secretion of optimedin in transfected cells. Optimedin and myocilin interact with each other in vitro as judged by the GST pulldown, co-immunoprecipitation and far-western binding assays. The C-terminal olfactomedin domains are essential for interaction between optimedin and myocilin, while the N-terminal domains of both proteins are involved in the formation of protein homodimers. We suggest that optimedin may be a candidate gene for disorders involving the anterior segment of the eye and the retina.
authors.affiliation: Laboratory of Molecular and Developmental Biology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Mario
authors.initials: M
authors.lastname: Torrado
authors.forename: Ritu
authors.initials: R
authors.lastname: Trivedi
authors.forename: Rina
authors.initials: R
authors.lastname: Zinovieva
authors.forename: Irina
authors.initials: I
authors.lastname: Karavanova
authors.forename: Stanislav I
authors.initials: SI
authors.lastname: Tomarev
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D019556:COS Cells; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D005123:Eye / Q000378:metabolism*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005901:Glaucoma / Q000235:genetics* / Q000378:metabolism; D006023:Glycoproteins / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism*; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D009928:Organ Specificity; D051381:Rats; D016415:Sequence Alignment; D000099179:Myocilin
chemical_list: D003598:Cytoskeletal Proteins; D016326:Extracellular Matrix Proteins; D005136:Eye Proteins; D006023:Glycoproteins; D000099179:Myocilin; C466064:OLFM3 protein, human; C466063:Olfm3 protein, rat; C081451:olfactomedin