title: The retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) links RPGR to the nephronophthisis protein network.
abstract: Nephronophthisis is a heterogenetic autosomal recessive disorder associated with multiple developmental abnormalities, including cystic kidney disease and retinal degeneration. Retinal dystrophies, in particular the X-linked forms, are believed to represent a distinct group of hereditary diseases; however, their genetic complexity and overlap with other syndromic diseases is increasingly apparent. In this study, we report that depletion of retinitis pigmentosa GTPase regulator (RPGR) during zebrafish embryogenesis causes developmental changes indistinguishable from the abnormalities caused by the depletion of nephrocystin-5 or nephrocystin-6. However, RPGR did not directly interact with either gene product. RPGR-interacting protein 1 was found to act as an adaptor connecting RPGR to nephrocystin-6, thereby linking it to the nephronophthisis protein network. This interaction was abolished by truncating mutations (c.1107delA) of the interacting protein. Our findings underline the importance of the interplay between the two protein networks, suggesting a phenotypic modulation in both retinitis pigmentosa and nephronophthisis.
authors.affiliation: University Hospital Freiburg, Hugstetter Strasse 55, Freiburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Gerner
authors.forename: Ramachandran
authors.initials: R
authors.lastname: Haribaskar
authors.forename: Michael
authors.initials: M
authors.lastname: Pütz
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Czerwitzki
authors.forename: Gerd
authors.initials: G
authors.lastname: Walz
authors.forename: Tobias
authors.initials: T
authors.lastname: Schäfer
mesh_terms: D000818:Animals; D005136:Eye Proteins; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012174:Retinitis Pigmentosa / Q000235:genetics* / Q000378:metabolism*; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins
chemical_list: D005136:Eye Proteins; D011506:Proteins; C551559:RPGRIP1 protein, zebrafish; D029961:Zebrafish Proteins; C547528:rpgra protein, zebrafish; D020558:GTP Phosphohydrolases