TY - JOUR T1 - Trafficking of Membrane-Associated Proteins to Cone Photoreceptor Outer Segments Requires the Chromophore 11-<em>cis</em>-Retinal JF - The Journal of Neuroscience JO - J. Neurosci. SP - 4008 LP - 4014 DO - 10.1523/JNEUROSCI.0317-08.2008 VL - 28 IS - 15 AU - Houbin Zhang AU - Jie Fan AU - Sha Li AU - Sukanya Karan AU - Baerbel Rohrer AU - Krzysztof Palczewski AU - Jeanne M. Frederick AU - Rosalie K. Crouch AU - Wolfgang Baehr Y1 - 2008/04/09 UR - http://www.jneurosci.org/content/28/15/4008.abstract N2 - Lecithin retinol acyl transferase (LRAT) and retinal pigment epithelium protein 65 (RPE65) are key enzymes of the retinoid cycle. In Lrat−/− and Rpe65−/− mice, models of human Leber congenital amaurosis, the retinoid cycle is disrupted and 11-cis-retinal, the chromophore of visual pigments, is not produced. The Lrat−/− and Rpe65−/− retina phenotype presents with rapid sectorial cone degeneration, and the visual pigments, S-opsin and M/L-opsin, fail to traffic to cone outer segments appropriately. In contrast, rod opsin traffics normally in mutant rods. Concomitantly, guanylate cyclase 1, cone Tα-subunit, cone phosphodiesterase 6α′ (PDE6α′), and GRK1 (G-protein-coupled receptor kinase 1; opsin kinase) are not transported to Lrat−/− and Rpe65−/− cone outer segments. Aberrant localization of these membrane-associated proteins was evident at postnatal day 15, before the onset of ventral and central cone degeneration. Protein levels of cone Tα and cone PDE6α′ were reduced, whereas their transcript levels were unchanged, suggesting posttranslational degradation. In an Rpe65−/−Rho−/− double knock-out model, trafficking of cone pigments and membrane-associated cone phototransduction polypeptides to the outer segments proceeded normally after 11-cis-retinal administration. These results suggest that ventral and central cone opsins must be regenerated with 11-cis-retinal to permit transport to the outer segments. Furthermore, the presence of 11-cis-retinal is essential for proper transport of several membrane-associated cone phototransduction polypeptides in these cones. ER -