Journal Article

TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein

Christina F. Chakarova, Hemant Khanna, Amna Z. Shah, Suresh B. Patil, Tina Sedmak, Carlos A. Murga-Zamalloa, Myrto G. Papaioannou, Kerstin Nagel-Wolfrum, Irma Lopez, Peter Munro, Michael Cheetham, Robert K. Koenekoop, Rosa M. Rios, Karl Matter, Uwe Wolfrum, Anand Swaroop and Shomi S. Bhattacharya

in Human Molecular Genetics

Volume 20, issue 5, pages 975-987
Published in print March 2011 | ISSN: 0964-6906
Published online December 2010 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddq543
TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein

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We recently reported that mutations in the widely expressed nuclear protein TOPORS (topoisomerase I-binding arginine/serine rich) are associated with autosomal dominant retinal degeneration. However, the precise localization and a functional role of TOPORS in the retina remain unknown. Here, we demonstrate that TOPORS is a novel component of the photoreceptor sensory cilium, which is a modified primary cilium involved with polarized trafficking of proteins. In photoreceptors, TOPORS localizes primarily to the basal bodies of connecting cilium and in the centrosomes of cultured cells. Morpholino-mediated silencing of topors in zebrafish embryos demonstrates in another species a comparable retinal problem as seen in humans, resulting in defective retinal development and failure to form outer segments. These defects can be rescued by mRNA encoding human TOPORS. Taken together, our data suggest that TOPORS may play a key role in regulating primary cilia-dependent photoreceptor development and function. Additionally, it is well known that mutations in other ciliary proteins cause retinal degeneration, which may explain why mutations in TOPORS result in the same phenotype.

Journal Article.  5935 words.  Illustrated.

Subjects: Genetics and Genomics

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