Retinitis Pigmentosa GTPase Regulator (RPGR) protein isoforms in mammalian retina: insights into X-linked Retinitis Pigmentosa and associated ciliopathies

Vision Res. 2008 Feb;48(3):366-76. doi: 10.1016/j.visres.2007.08.005. Epub 2007 Sep 27.


Mutations in the cilia-centrosomal protein Retinitis Pigmentosa GTPase Regulator (RPGR) are a frequent cause of retinal degeneration. The RPGR gene undergoes complex alternative splicing and encodes multiple protein isoforms. To elucidate the function of major RPGR isoforms (RPGR 1-19 and RPGR ORF15), we have generated isoform-specific antibodies and examined their expression and localization in the retina. Using sucrose-gradient centrifugation, immunofluorescence and co-immunoprecipitation methods, we show that RPGR isoforms localize to distinct sub-cellular compartments in mammalian photoreceptors and associate with a number of cilia-centrosomal proteins. The RCC1-like domain of RPGR, which is present in all major RPGR isoforms, is sufficient to target it to the cilia and centrosomes in cultured cells. Our findings indicate that multiple isotypes of RPGR may perform overlapping yet somewhat distinct transport-related functions in photoreceptors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Cattle
  • Cell Cycle / physiology
  • Cells, Cultured
  • Centrosome / metabolism
  • Eye Diseases, Hereditary / genetics*
  • Eye Diseases, Hereditary / metabolism
  • Eye Proteins / genetics
  • Eye Proteins / immunology
  • Eye Proteins / metabolism
  • Eye Proteins / physiology*
  • Genetic Diseases, X-Linked / genetics*
  • Genetic Diseases, X-Linked / metabolism
  • Humans
  • Mice
  • Photoreceptor Cells, Vertebrate / metabolism
  • Protein Isoforms / metabolism
  • Protein Isoforms / physiology
  • Retina / metabolism
  • Retinitis Pigmentosa / genetics*
  • Retinitis Pigmentosa / metabolism
  • Species Specificity


  • Carrier Proteins
  • Eye Proteins
  • Protein Isoforms
  • RPGR protein, mouse