PUBLICATION
TOPORS, Implicated in Retinal Degeneration, is a Cilia-Centrosomal Protein
- Authors
- Chakarova, C.F., Khanna, H., Shah, A.Z., Patil, S.B., Sedmak, T., Murga-Zamalloa, C.A., Papaioannou, M.G., Nagel-Wolfrum, K., Lopez, I., Munro, P., Cheetham, M., Koenekoop, R.K., Rios, R.M., Matter, K., Wolfrum, U., Swaroop, A., and Bhattacharya, S.S.
- ID
- ZDB-PUB-101222-34
- Date
- 2011
- Source
- Human molecular genetics 20(5): 975-987 (Journal)
- Registered Authors
- Khanna, Hemant
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line
- Cells, Cultured
- Centrosome/metabolism*
- Cilia/genetics
- Cilia/metabolism*
- Humans
- Mice
- Neoplasm Proteins/genetics
- Neoplasm Proteins/metabolism*
- Nuclear Proteins/genetics
- Nuclear Proteins/metabolism*
- Photoreceptor Cells/metabolism
- Protein Transport
- Retina/metabolism
- Retinal Degeneration/genetics
- Retinal Degeneration/metabolism*
- Ubiquitin-Protein Ligases/genetics
- Ubiquitin-Protein Ligases/metabolism*
- Zebrafish
- PubMed
- 21159800 Full text @ Hum. Mol. Genet.
Citation
Chakarova, C.F., Khanna, H., Shah, A.Z., Patil, S.B., Sedmak, T., Murga-Zamalloa, C.A., Papaioannou, M.G., Nagel-Wolfrum, K., Lopez, I., Munro, P., Cheetham, M., Koenekoop, R.K., Rios, R.M., Matter, K., Wolfrum, U., Swaroop, A., and Bhattacharya, S.S. (2011) TOPORS, Implicated in Retinal Degeneration, is a Cilia-Centrosomal Protein. Human molecular genetics. 20(5):975-987.
Abstract
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 localisation 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 localises 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping