Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa

Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8840-4. doi: 10.1073/pnas.88.19.8840.

Abstract

Thirteen mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa (ADRP) have been produced by transfection of cloned cDNA into tissue culture cells. Three mutants [class I: Phe-45----Leu, Gln-344----termination (deletion of C-terminal positions 344-348), and Pro-347----Leu] resemble wild-type rhodopsin in yield, regenerability with 11-cis-retinal, and plasma membrane localization. Ten mutants [class II: Thr-17----Met, Pro-23----His, Thr-58----Arg, Val-87----Asp, Gly-89----Asp, Gly-106----Trp, Arg-135----Leu, Arg-135----Trp, Tyr-178----Cys, and Asp-190----Gly] accumulate to significantly lower levels, regenerate with 11-cis-retinal variably or not at all, and are transported inefficiently to the plasma membrane, remaining primarily in the endoplasmic reticulum. These data suggest that there are at least two distinct biochemical defects associated with different rhodopsin mutants in ADRP.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Blotting, Western
  • Cell Compartmentation
  • Cells, Cultured
  • Cloning, Molecular
  • DNA Mutational Analysis
  • Genes, Dominant
  • Glycosylation
  • Humans
  • Microscopy, Electron
  • Molecular Structure
  • Protein Processing, Post-Translational
  • Retinitis Pigmentosa / genetics*
  • Rhodopsin / chemistry
  • Rhodopsin / genetics*
  • Rhodopsin / physiology
  • Spectrum Analysis

Substances

  • Rhodopsin