Journal
HUMAN MOLECULAR GENETICS
Volume 15, Issue 11, Pages 1847-1857Publisher
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddl107
Keywords
-
Funding
- NCRR NIH HHS [P40 RR001183, RR 01183] Funding Source: Medline
- NEI NIH HHS [R01 EY007042-20, R01 EY007961, R01 EY007042, EY 07003, EY 13408, P30 EY012598, R01 EY007758, EY 12598, EY 07961, EY 07758, R01 EY013408, F31 EY007003, P30 EY007003] Funding Source: Medline
- NIDDK NIH HHS [DK 10683-06, P60 DK020572, P30 DK020572, R01 DK064614, DK 064614, DK 20572, DK 1069274] Funding Source: Medline
Ask authors/readers for more resources
Centrosome- and cilia-associated proteins play crucial roles in establishing polarity and regulating intracellular transport in post-mitotic cells. Using genetic mapping and positional candidate strategy, we have identified an in-frame deletion in a novel centrosomal protein CEP290 (also called NPHP6), leading to early-onset retinal degeneration in a newly identified mouse mutant, rd16. We demonstrate that CEP290 localizes primarily to centrosomes of dividing cells and to the connecting cilium of retinal photoreceptors. We show that, in the retina, CEP290 associates with several microtubule-based transport proteins including RPGR, which is mutated in similar to 15% of patients with retinitis pigmentosa. A truncated CEP290 protein (Delta CEP290) is detected in the rd16 retina, but in considerably reduced amounts; however, the mutant protein exhibits stronger association with specific RPGR isoform(s). Immunogold labeling studies demonstrate the redistribution of RPGR and of phototransduction proteins in the photoreceptors of rd16 retina. Our findings suggest a critical function for CEP290 in ciliary transport and provide insights into the mechanism of early-onset photoreceptor degeneration.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available