The retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) links RPGR to the nephronophthisis protein network.
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.
Gerner
Martin
M
University Hospital Freiburg, Hugstetter Strasse 55, Freiburg, Germany.
Haribaskar
Ramachandran
R
Pütz
Michael
M
Czerwitzki
Jacqueline
J
Walz
Gerd
G
Schäfer
Tobias
T
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
D005136:Eye Proteins; D011506:Proteins; C551559:RPGRIP1 protein, zebrafish; D029961:Zebrafish Proteins; C547528:rpgra protein, zebrafish; D020558:GTP Phosphohydrolases