| First Author | Insinna C | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 23 | Pages | 8094-104 |
| PubMed ID | 22674284 | Mgi Jnum | J:185275 |
| Mgi Id | MGI:5428059 | Doi | 10.1523/JNEUROSCI.0131-12.2012 |
| Citation | Insinna C, et al. (2012) An S-Opsin Knock-In Mouse (F81Y) Reveals a Role for the Native Ligand 11-cis-Retinal in Cone Opsin Biosynthesis. J Neurosci 32(23):8094-104 |
| abstractText | 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 approximately 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. |
