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An S-opsin knock-in mouse (F81Y) reveals a role for the native ligand 11-cis-retinal in cone opsin biosynthesis.

In absence of their natural ligand, 11-cis-retinal, cone opsin G-protein-coupled receptors fail to traffic normally, a condition associated with photoreceptor degeneration and blindness. We created a mouse with a point mutation (F81Y) in cone S-opsin. As expected, cones with this knock-in mutation respond to light with maximal sensitivity red-shifted from 360 to 420 nm, consistent with an altered interaction between the apoprotein and ligand, 11-cis-retinal. However, cones expressing F81Y S-opsin showed an ∼3-fold reduced absolute sensitivity that was associated with a corresponding reduction in S-opsin protein expression. The reduced S-opsin expression did not arise from decreased S-opsin mRNA or cone degeneration, but rather from enhanced endoplasmic reticulum (ER)-associated degradation of the nascent protein. Exogenously increased 11-cis-retinal restored F81Y S-opsin protein expression to normal levels, suggesting that ligand binding in the ER facilitates proper folding. Immunohistochemistry and electron microscopy of normal retinas showed that Mueller cells, which synthesize a precursor of 11-cis-retinal, are closely adjoined to the cone ER, so they could deliver the ligand to the site of opsin synthesis. Together, these results suggest that the binding of 11-cis-retinal in the ER is important for normal folding during cone opsin biosynthesis.

Pubmed ID: 22674284


  • Insinna C
  • Daniele LL
  • Davis JA
  • Larsen DD
  • Kuemmel C
  • Wang J
  • Nikonov SS
  • Knox BE
  • Pugh EN


The Journal of neuroscience : the official journal of the Society for Neuroscience

Publication Data

June 6, 2012

Associated Grants

  • Agency: NEI NIH HHS, Id: EY02660
  • Agency: NEI NIH HHS, Id: R01 EY002660

Mesh Terms

  • Algorithms
  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Electrophysiological Phenomena
  • Endoplasmic Reticulum
  • Fluorescent Antibody Technique
  • Immunohistochemistry
  • Immunoprecipitation
  • Light
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Electron
  • Mutation
  • Opsins
  • Real-Time Polymerase Chain Reaction
  • Receptors, G-Protein-Coupled
  • Retinal Cone Photoreceptor Cells
  • Retinal Rod Photoreceptor Cells
  • Retinaldehyde