期刊
HUMAN MOLECULAR GENETICS
卷 20, 期 5, 页码 975-987出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddq543
关键词
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资金
- Foundation Fighting Blindness, EVI-GENORET [LSHG-CT-2005-512036]
- The Special Trustees of Moorfields Eye Hospital London
- National Institute of Health Research (UK)
- Biomedical Research Centre for Ophthalmology, Fight for Sight (UK)
- Midwest Eye Banks and Transplantation Center, National Institutes of Health [EY007961]
- Foundation Fighting Blindness, Biotechnology and Biological Sciences Research Council
- Foundation Fighting Blindness-Canada
- Fonds de la Recherche en Santee du Quebec
- Deutsche Forschungsgemeinschaft (DFG)
- FAUN-Stiftung, Nuermberg
- EU
- Gradiertenforderung of the Johannes Gutenberg University of Mainz, Germany
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.
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