Publication
Title
Nephrocystin-5, a ciliary IQ domain protein, is mutated in Senior-Loken syndrome and interacts with RPGR and calmodulin
Author
Abstract
Nephronophthisis (NPHP) is the most frequent genetic cause of chronic renal failure in children(1-3). Identification of four genes mutated in NPHP subtypes 1- 4 (refs. 4- 9) has linked the pathogenesis of NPHP to ciliary functions(9). 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.
Language
English
Source (journal)
Nature genetics. - New York, N.Y.
Publication
New York, N.Y. : 2005
ISSN
1061-4036
Volume/pages
37 :3 (2005) , p. 282-288
ISI
000227297800019
Full text (Publisher's DOI)
UAntwerpen
Publication type
Subject
External links
Web of Science
Record
Identification
Creation 05.11.2018
Last edited 04.09.2021