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Human Molecular Genetics, 2002, Vol. 11, No. 11 1291-1301
© 2002 Oxford University Press

Optimedin: a novel olfactomedin-related protein that interacts with myocilin

Mario Torrado1,{dagger}, Ritu Trivedi1, Rina Zinovieva1,{ddagger}, Irina Karavanova2 and Stanislav I. Tomarev1,*

1Laboratory of Molecular and Developmental Biology, National Eye Institute and 2Section of Molecular Neurobiology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA

Received January 22, 2002; Accepted March 14, 2002

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.

* To whom correspondence should be addressed. Tel: +1 301 496 8524; Fax: +1 301 496 8760; Email: tomarevs{at}nei.nih.gov

{dagger} Present address: Institute of Health Sciences, University of La Coruna, Campus de Oza, Edificio El Fortin, La Coruna 15006, Spain.

{ddagger} Present address: N.K. Koltzov Institute of Developmental Biology, Russian Academy of Sciences, Moscow, Russia.


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