PMID:21159800

Citation	Chakarova, CF, Khanna, H, Shah, AZ, Patil, SB, Sedmak, T, Murga-Zamalloa, CA, Papaioannou, MG, Nagel-Wolfrum, K, Lopez, I, Munro, P, Cheetham, M, Koenekoop, RK, Rios, RM, Matter, K, Wolfrum, U, Swaroop, A and Bhattacharya, SS (2011) TOPORS, implicated in retinal degeneration, is a cilia-centrosomal protein. Hum. Mol. Genet. 20:975-87
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.
Links	PubMed PMC3033188 Online version:10.1093/hmg/ddq543
Keywords	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
edit table

Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
DANRE:A0JMC0	involved_in	GO:0010842: retina layer formation	ECO:0000315: mutant phenotype evidence used in manual assertion	ZFIN:ZDB-MRPHLNO-110331-5	P		Seeded From UniProt	complete
DANRE:E7F1A2	involved_in	GO:0010842: retina layer formation	ECO:0000315: mutant phenotype evidence used in manual assertion	ZFIN:ZDB-MRPHLNO-110331-5	P		Seeded From UniProt	complete
BOVIN:F1N329	located_in	GO:0005813: centrosome	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
BOVIN:F1N329	enables	GO:0043015: gamma-tubulin binding	ECO:0000314: direct assay evidence used in manual assertion		F		Seeded From UniProt	complete
DANRE:F1QSD4	involved_in	GO:0010842: retina layer formation	ECO:0000315: mutant phenotype evidence used in manual assertion	ZFIN:ZDB-MRPHLNO-110331-5	P		Seeded From UniProt	complete
PIG:F1SE69	located_in	GO:0032391: photoreceptor connecting cilium	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
DANRE:Q5BLE0	involved_in	GO:0010842: retina layer formation	ECO:0000315: mutant phenotype evidence used in manual assertion	ZFIN:ZDB-MRPHLNO-110331-5	P		Seeded From UniProt	complete
DANRE:Q5BLE0	involved_in	GO:0043066: negative regulation of apoptotic process	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DANRE:Q5BLE0	involved_in	GO:0046548: retinal rod cell development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DANRE:Q5BLE0	involved_in	GO:0046549: retinal cone cell development	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DANRE:Q5BLE0	involved_in	GO:0010842: retina layer formation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
DANRE:Q5BLE0	involved_in	GO:0035845: photoreceptor cell outer segment organization	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete
MOUSE:TOPRS	located_in	GO:0032391: photoreceptor connecting cilium	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
MOUSE:TOPRS	located_in	GO:0005634: nucleus	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(CL:0000740)	Seeded From UniProt	complete
MOUSE:TOPRS	located_in	GO:0036064: ciliary basal body	ECO:0000314: direct assay evidence used in manual assertion		C	part_of:(CL:0000210)	Seeded From UniProt	complete
HUMAN:TOPRS	located_in	GO:0000922: spindle pole	ECO:0000314: direct assay evidence used in manual assertion		C	existence_overlaps:(GO:0000278)	Seeded From UniProt	complete
HUMAN:TOPRS	located_in	GO:0005814: centriole	ECO:0000314: direct assay evidence used in manual assertion		C	existence_overlaps:(GO:0000080)|existence_overlaps:(GO:0000084)|existence_overlaps:(GO:0000085)	Seeded From UniProt	complete
HUMAN:TOPRS	located_in	GO:0032391: photoreceptor connecting cilium	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TOPRS	part_of	GO:0000930: gamma-tubulin complex	ECO:0000314: direct assay evidence used in manual assertion		C	existence_overlaps:(GO:0000080)|existence_overlaps:(GO:0000084)|existence_overlaps:(GO:0000085)	Seeded From UniProt	complete
HUMAN:TOPRS	colocalizes_with	GO:0016605: PML body	ECO:0000314: direct assay evidence used in manual assertion		C	existence_overlaps:(GO:0000080)|existence_overlaps:(GO:0000084)|existence_overlaps:(GO:0000085)	Seeded From UniProt	complete
HUMAN:TOPRS	located_in	GO:0036064: ciliary basal body	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TOPRS	located_in	GO:0030496: midbody	ECO:0000304: author statement supported by traceable reference used in manual assertion		C	existence_overlaps:(GO:0051326)	Seeded From UniProt	complete
HUMAN:TOPRS	part_of	GO:0000922: spindle pole	ECO:0000314: direct assay evidence used in manual assertion		C	exists_during:(GO:0000278)	Seeded From UniProt	complete
HUMAN:TOPRS	part_of	GO:0030496: midbody	ECO:0000304: author statement supported by traceable reference used in manual assertion		C	exists_during:(GO:0051326)	Seeded From UniProt	complete
HUMAN:TOPRS	colocalizes_with	GO:0005868: cytoplasmic dynein complex	ECO:0000304: author statement supported by traceable reference used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TOPRS	part_of	GO:0000930: gamma-tubulin complex	ECO:0000314: direct assay evidence used in manual assertion		C	exists_during:(GO:0000080)|exists_during:(GO:0000084)|exists_during:(GO:0000085)	Seeded From UniProt	complete
HUMAN:TOPRS	part_of	GO:0005814: centriole	ECO:0000314: direct assay evidence used in manual assertion		C	exists_during:(GO:0000080)|exists_during:(GO:0000084)|exists_during:(GO:0000085)	Seeded From UniProt	complete
HUMAN:TOPRS	involved_in	GO:0010842: retina layer formation	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q5BLE0	P		Seeded From UniProt	complete
HUMAN:TOPRS	colocalizes_with	GO:0016605: PML body	ECO:0000314: direct assay evidence used in manual assertion		C	exists_during:(GO:0000080)|exists_during:(GO:0000084)|exists_during:(GO:0000085)	Seeded From UniProt	complete
HUMAN:TOPRS	part_of	GO:0032391: photoreceptor connecting cilium	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TOPRS	involved_in	GO:0035845: photoreceptor cell outer segment organization	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q5BLE0	P		Seeded From UniProt	complete
HUMAN:TOPRS	part_of	GO:0036064: ciliary basal body	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:TOPRS	involved_in	GO:0046548: retinal rod cell development	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q5BLE0	P		Seeded From UniProt	complete
HUMAN:TOPRS	involved_in	GO:0043066: negative regulation of apoptotic process	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q5BLE0	P		Seeded From UniProt	complete
HUMAN:TOPRS	involved_in	GO:0046549: retinal cone cell development	ECO:0000250: sequence similarity evidence used in manual assertion	UniProtKB:Q5BLE0	P		Seeded From UniProt	complete

References

See Help:References for how to manage references in GONUTS.