Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin
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- 20 February 2005
- journal article
- letter
- Published by Springer Nature in Nature Genetics
- Vol. 37 (3) , 282-288
- https://doi.org/10.1038/ng1520
Abstract
Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal failure in children1,2,3. Identification of four genes mutated in NPHP subtypes 1–4 (refs. 4, 5, 6, 7, 8, 9) has linked the pathogenesis of NPHP to ciliary functions9. Ten percent of affected individuals have retinitis pigmentosa, constituting the renal-retinal Senior-Loken syndrome (SLSN). Here we identify, by positional cloning, mutations in an evolutionarily conserved gene, IQCB1 (also called NPHP5), as the most frequent cause of SLSN. IQCB1 encodes an IQ-domain protein, nephrocystin-5. All individuals with IQCB1 mutations have retinitis pigmentosa. Hence, we examined the interaction of nephrocystin-5 with RPGR (retinitis pigmentosa GTPase regulator), which is expressed in photoreceptor cilia and associated with 10–20% of retinitis pigmentosa. We show that nephrocystin-5, RPGR and calmodulin can be coimmunoprecipitated from retinal extracts, and that these proteins localize to connecting cilia of photoreceptors and to primary cilia of renal epithelial cells. Our studies emphasize the central role of ciliary dysfunction in the pathogenesis of SLSN.Keywords
This publication has 19 references indexed in Scilit:
- Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determinationNature Genetics, 2003
- Mutations in a novel gene, NPHP3, cause adolescent nephronophthisis, tapeto-retinal degeneration and hepatic fibrosisNature Genetics, 2003
- RPGR Isoforms in Photoreceptor Connecting Cilia and the Transitional Zone of Motile CiliaInvestigative Opthalmology & Visual Science, 2003
- The Draft Genome of Ciona intestinalis : Insights into Chordate and Vertebrate OriginsScience, 2002
- A Gene Mutated in Nephronophthisis and Retinitis Pigmentosa Encodes a Novel Protein, Nephroretinin, Conserved in EvolutionAmerican Journal of Human Genetics, 2002
- The gene mutated in juvenile nephronophthisis type 4 encodes a novel protein that interacts with nephrocystinNature Genetics, 2002
- The left-right determinant inversin has highly conserved ankyrin repeat and IQ domains and interacts with calmodulinHuman Genetics, 2002
- NephrocystinJournal of the American Society of Nephrology, 2000
- A novel gene that encodes a protein with a putative src homology 3 domain is a candidate gene for familial juvenile nephronophthisisHuman Molecular Genetics, 1997
- A novel gene encoding an SH3 domain protein is mutated in nephronophthisis type 1Nature Genetics, 1997