PUBLICATION

The retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) links RPGR to the nephronophthisis protein network

Authors
Gerner, M., Haribaskar, R., Pütz, M., Czerwitzki, J., Walz, G., and Schäfer, T.
ID
ZDB-PUB-100309-16
Date
2010
Source
Kidney International   77(10): 891-896 (Journal)
Registered Authors
Keywords
cell and transport physiology, cell signaling, familial nephropathy, genetics and development, genetic renal disease
MeSH Terms
  • Animals
  • Eye Proteins
  • GTP Phosphohydrolases/genetics
  • GTP Phosphohydrolases/metabolism
  • Mutation*
  • Proteins/genetics*
  • Proteins/metabolism*
  • Retinitis Pigmentosa/genetics*
  • Retinitis Pigmentosa/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism
  • Zebrafish Proteins
PubMed
20200501 Full text @ Kidney Int.
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.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping