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Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species.

Publication ,  Journal Article
Mavlyutov, TA; Zhao, H; Ferreira, PA
Published in: Hum Mol Genet
August 1, 2002

The retinitis pigmentosa GTPase regulator (RPGR) is encoded by the X-linked RP3 locus, which upon genetic lesions leads to neurodegeneration of photoreceptors and blindness. The findings that RPGR specifically and directly interacts in vivo and in vitro with retina-specific RPGR-interacting protein 1 (RPGRIP) and that human mutations in RPGR uncouple its interaction with RPGRIP provided the first clue for the retina-specific pathogenesis of X-linked RP3. Recently, mutations in RPGRIP were found to lead to the retinal dystrophy, Leber congenital amaurosis. However, mouse models null for RPGR had, surprisingly, a very mild phenotype compared with those observed in XlRP3-affected humans and dogs. Moreover, recent reports are seemingly in disagreement on the localization of RPGR and RPGRIP in photoreceptors. These discrepancies were compounded with the finding of RPGR mutations leading exclusively to X-linked cone dystrophy. To resolve these discrepancies and to gain further insight into the pathology associated with RPGR- and RPGRIP-allied retinopathies, we now show, using several isoform-specific antibodies, that RPGR and RPGRIP isoforms are distributed and co-localized at restricted foci throughout the outer segments of human and bovine, but not mice rod photoreceptors. In humans, they also localize in cone outer segments. RPGRIP is also expressed in other neurons such as amacrine cells. Thus, the data lend support to the existence of species-specific subcellular processes governing the function and/or organization of the photoreceptor outer segment as reflected by the species-specific localization of RPGR and RPGRIP protein isoforms in this compartment, and provide a rationale for the disparity of phenotypes among species and in the human.

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Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

August 1, 2002

Volume

11

Issue

16

Start / End Page

1899 / 1907

Location

England

Related Subject Headings

  • Subcellular Fractions
  • Species Specificity
  • Rod Cell Outer Segment
  • Retinitis Pigmentosa
  • Retina
  • Proteins
  • Photoreceptor Cells, Vertebrate
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice
 

Citation

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Mavlyutov, T. A., Zhao, H., & Ferreira, P. A. (2002). Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species. Hum Mol Genet, 11(16), 1899–1907. https://doi.org/10.1093/hmg/11.16.1899
Mavlyutov, Timur A., Haiyan Zhao, and Paulo A. Ferreira. “Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species.Hum Mol Genet 11, no. 16 (August 1, 2002): 1899–1907. https://doi.org/10.1093/hmg/11.16.1899.
Mavlyutov, Timur A., et al. “Species-specific subcellular localization of RPGR and RPGRIP isoforms: implications for the phenotypic variability of congenital retinopathies among species.Hum Mol Genet, vol. 11, no. 16, Aug. 2002, pp. 1899–907. Pubmed, doi:10.1093/hmg/11.16.1899.
Journal cover image

Published In

Hum Mol Genet

DOI

ISSN

0964-6906

Publication Date

August 1, 2002

Volume

11

Issue

16

Start / End Page

1899 / 1907

Location

England

Related Subject Headings

  • Subcellular Fractions
  • Species Specificity
  • Rod Cell Outer Segment
  • Retinitis Pigmentosa
  • Retina
  • Proteins
  • Photoreceptor Cells, Vertebrate
  • Molecular Sequence Data
  • Mice, Inbred C57BL
  • Mice