title: TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein.
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 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.
authors.affiliation: Institute of Ophthalmology, UCL, London EC1V 9EL, UK.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Chakarova
authors.forename: Hemant
authors.initials: H
authors.lastname: Khanna
authors.forename: Amna Z
authors.initials: AZ
authors.lastname: Shah
authors.forename: Suresh B
authors.initials: SB
authors.lastname: Patil
authors.forename: Tina
authors.initials: T
authors.lastname: Sedmak
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Murga-Zamalloa
authors.forename: Myrto G
authors.initials: MG
authors.lastname: Papaioannou
authors.forename: Kerstin
authors.initials: K
authors.lastname: Nagel-Wolfrum
authors.forename: Irma
authors.initials: I
authors.lastname: Lopez
authors.forename: Peter
authors.initials: P
authors.lastname: Munro
authors.forename: Michael
authors.initials: M
authors.lastname: Cheetham
authors.forename: Robert K
authors.initials: RK
authors.lastname: Koenekoop
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Rios
authors.forename: Karl
authors.initials: K
authors.lastname: Matter
authors.forename: Uwe
authors.initials: U
authors.lastname: Wolfrum
authors.forename: Anand
authors.initials: A
authors.lastname: Swaroop
authors.forename: Shomi S
authors.initials: SS
authors.lastname: Bhattacharya
mesh_terms: D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010786:Photoreceptor Cells / Q000378:metabolism; D021381:Protein Transport; D012160:Retina / Q000378:metabolism; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; C120157:TOPORS protein, human; D044767:Ubiquitin-Protein Ligases