In-frame deletion in a novel centrosomal/ciliary protein CEP290/NPHP6 perturbs its interaction with RPGR and results in early-onset retinal degeneration in the rd16 mouse.

Human Molecular Genetics
Bo ChangAnand Swaroop

Abstract

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 approximately 15% of patients with retinitis pigmentosa. A truncated CEP290 protein (DeltaCEP290) 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.

References

Nov 26, 1996·Proceedings of the National Academy of Sciences of the United States of America·T LiT P Dryja
Dec 2, 1999·Nature Genetics·T FurukawaC L Cepko
Mar 22, 2000·Proceedings of the National Academy of Sciences of the United States of America·D H HongT Li
May 11, 2000·Proceedings of the National Academy of Sciences of the United States of America·N B AkhmedovD B Farber
Aug 10, 2000·Nature Genetics·R VervoortA F Wright
Apr 3, 2001·American Journal of Human Genetics·T P DryjaE L Berson
Sep 5, 2001·Nature Reviews. Molecular Cell Biology·S Doxsey
Nov 6, 2001·Nature Genetics·A J MearsA Swaroop
Feb 21, 2002·Vision Research·B ChangJ R Heckenlively
Mar 28, 2002·The Journal of Cell Biology·Gregory J PazourJoseph C Besharse
Oct 31, 2002·The Journal of Cell Biology·Alexander Dammermann, Andreas Merdes
Jan 9, 2003·Current Opinion in Cell Biology·Janine Beisson, Michel Wright
Mar 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yun ZhaoTiansen Li
May 27, 2003·Investigative Ophthalmology & Visual Science·Dong-Hyun HongTiansen Li
Oct 18, 2003·American Journal of Human Genetics·Dror SharonEliot L Berson
Jun 3, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kirk MykytynVal C Sheffield
Jul 1, 2004·PLoS Biology·Seth BlackshawConstance L Cepko
Jul 23, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Qin LiuEric A Pierce
Oct 12, 2004·Biochemical and Biophysical Research Communications·Jianhui GuoChengchao Shou
Nov 13, 2004·Proceedings of the National Academy of Sciences of the United States of America·Darryl Y NishimuraVal C Sheffield
Mar 2, 2005·Nature Reviews. Genetics·Jose L BadanoNicholas Katsanis
Jun 15, 2005·Annual Review of Biochemistry·Kim Nasmyth, Christian H Haering
Dec 8, 2005·Visual Neuroscience·B ChangJ R Heckenlively
Mar 1, 2006·Proceedings of the National Academy of Sciences of the United States of America·Masayuki AkimotoAnand Swaroop

❮ Previous
Next ❯

Citations

Feb 2, 2008·Histochemistry and Cell Biology·Jantina A ManningSharad Kumar
Jul 24, 2010·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Matthias T F Wolf, Friedhelm Hildebrandt
Jan 7, 2011·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Aoife M Waters, Philip L Beales
Oct 1, 2010·Neurochemical Research·Monica M JablonskiEldon E Geisert
Jan 13, 2011·European Journal of Human Genetics : EJHG·Lorena Fernández-MartínezFrancesca Pasutto
Nov 12, 2009·Molecular Therapy : the Journal of the American Society of Gene Therapy·Zhijian WuPeter Colosi
May 12, 2009·Nature Genetics·Hemant KhannaNicholas Katsanis
Jun 5, 2007·Nature Genetics·Anneke I den HollanderRonald Roepman
May 31, 2011·Nature Medicine·Madeline A LancasterJoseph G Gleeson
Jan 19, 2012·Biologie aujourd'hui·Cathy Fisch, Pascale Dupuis-Williams
Apr 22, 2011·The New England Journal of Medicine·Friedhelm HildebrandtNicholas Katsanis
Aug 18, 2010·Proceedings of the National Academy of Sciences of the United States of America·James S FriedmanAnand Swaroop
Oct 3, 2012·Proceedings of the National Academy of Sciences of the United States of America·Andrea AguilarNathalie Spassky
May 15, 2007·Molecular & Cellular Proteomics : MCP·Qin LiuEric A Pierce
Jun 4, 2010·Molecular Biology of the Cell·Sebastian PatzkeTrond Stokke
May 2, 2009·Chemical Senses·Paul M JenkinsJeffrey R Martens
Aug 30, 2008·Human Molecular Genetics·Tobias SchäferGerd Walz
Sep 25, 2009·Human Molecular Genetics·Scott D WeatherbeeKathryn V Anderson
Dec 17, 2010·Human Molecular Genetics·Christina F ChakarovaShomi S Bhattacharya
Feb 2, 2011·Human Molecular Genetics·Pamela R PretoriusDiane C Slusarski
Sep 22, 2011·Human Molecular Genetics·Milica GakovicAlan F Wright
Jul 31, 2012·Human Molecular Genetics·Alejandro Estrada-CuzcanoDorus A Mans
Aug 15, 2013·Human Molecular Genetics·Yan ZhangVal C Sheffield
Jul 10, 2007·Journal of Medical Genetics·Juliana HelouFriedhelm Hildebrandt
Mar 12, 2009·Nephron. Physiology·Iben R VelandSøren T Christensen
Nov 13, 2010·Nephron. Experimental Nephrology·Toby W Hurd, Friedhelm Hildebrandt
Mar 16, 2013·Investigative Ophthalmology & Visual Science·Justin P TempletonEldon E Geisert
Apr 17, 2008·The Journal of Clinical Investigation·Mariacarmela AlloccaAlberto Auricchio
Mar 3, 2009·The Journal of Clinical Investigation·Norann A Zaghloul, Nicholas Katsanis
Sep 3, 2010·The Journal of Clinical Investigation·Anneke I den HollanderFrans P M Cremers

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.