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The retinitis pigmentosa GTPase regulator (RPGR) interacts with novel transport-like proteins in the outer segments of rod photoreceptors.

Mutations in the retinitis pigmentosa GTPase regulator (RPGR) gene cause X-linked retinitis pigmentosa type 3 (RP3), a severe, progressive and degenerative retinal dystrophy eventually leading to complete blindness. RPGR is ubiquitously expressed, yet mutations in the RPGR gene lead to a retina-restricted phenotype. To date, all RP3 associated missense mutations that have been identified are located in the RCC1-homologous domain (RHD) of RPGR. To investigate the molecular pathogenesis of RP3, we screened retinal yeast two-hybrid libraries with the RHD of RPGR. We identified several alternatively spliced gene products, some with retina-restricted expression, that interact specifically with RPGR in vivo and in vitro. Thus, these proteins were named RPGR-interacting protein 1 (RPGRIP1) isoforms. They contain a C-terminal RPGR-interacting domain and stretches of variable coiled-coil domains homologous to proteins involved in vesicular trafficking. The interaction between RPGR and RPGRIP1 isoforms was impaired in vivo by RP3-associated mutations in RPGR. Moreover, RPGR and RPGRIP1 co-localize in the outer segment of rod photoreceptors, which is in full agreement with the retinitis pigmentosa phenotype observed in RP3 patients. The localization of RPGRIP1 at 14q11 makes it a strong candidate gene for RP16. These results provide a clue for the retina-specific pathogenesis in RP3, and hint towards the involvement of RPGR and RPGRIP1 in mediating vesicular transport-associated processes.

Pubmed ID: 10958648


  • Roepman R
  • Bernoud-Hubac N
  • Schick DE
  • Maugeri A
  • Berger W
  • Ropers HH
  • Cremers FP
  • Ferreira PA


Human molecular genetics

Publication Data

September 1, 2000

Associated Grants

  • Agency: NEI NIH HHS, Id: R01 EY011993
  • Agency: NEI NIH HHS, Id: R01 EY012665

Mesh Terms

  • 3' Untranslated Regions
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Blotting, Northern
  • Blotting, Western
  • Carrier Proteins
  • Cattle
  • Cell-Free System
  • Chromosomes, Human, Pair 14
  • Eye Proteins
  • Glutathione Transferase
  • Humans
  • Immunohistochemistry
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Mutation, Missense
  • Phenotype
  • Plasmids
  • Precipitin Tests
  • Protein Biosynthesis
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Proteins
  • Retina
  • Retinal Rod Photoreceptor Cells
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Temperature
  • Tissue Distribution
  • Transcriptional Activation
  • Two-Hybrid System Techniques