NinaB Is Essential for Drosophila Vision but Induces Retinal Degeneration in Opsin-deficient Photoreceptors |
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Authors: | Olaf Voolstra Vitus Oberhauser Emerich Sumser Nina E Meyer Michael E Maguire Armin Huber Johannes von Lintig |
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Institution: | From the ‡Institut für Biologie I, Neurobiologie und Tiephysiologie, Albert-Ludwigs Universität, D-79102 Freiburg, Germany, ;the §Institut für Physiologie and Biosensorik, Universität Hohenheim, D-70599 Hohenheim, Germany, and ;the ¶Department of Pharmacology, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44160 |
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Abstract: | In animals, visual pigments are essential for photoreceptor function and survival. These G-protein-coupled receptors consist of a protein moiety (opsin) and a covalently bound 11-cis-retinylidene chromophore. The chromophore is derived from dietary carotenoids by oxidative cleavage and trans-to-cis isomerization of double bonds. In vertebrates, the necessary chemical transformations are catalyzed by two distinct but structurally related enzymes, the carotenoid oxygenase β-carotenoid-15,15′-monooxygenase and the retinoid isomerase RPE65 (retinal pigment epithelium protein of 65 kDa). Recently, we provided biochemical evidence that these reactions in insects are catalyzed by a single enzyme family member named NinaB. Here we show that in the fly pathway, carotenoids are mandatory precursors of the chromophore. After chromophore formation, the retinoid-binding protein Pinta acts downstream of NinaB and is required to supply photoreceptors with chromophore. Like ninaE encoding the opsin, ninaB expression is eye-dependent and is activated as a downstream target of the eyeless/pax6 and sine oculis master control genes for eye development. The requirement for coordinated synthesis of chromophore and opsin is evidenced by analysis of ninaE mutants. Retinal degeneration in opsin-deficient photoreceptors is caused by the chromophore and can be prevented by restricting its supply as seen in an opsin and chromophore-deficient double mutant. Thus, our study identifies NinaB as a key component for visual pigment production and provides evidence that chromophore in opsin-deficient photoreceptors can elicit retinal degeneration. |
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Keywords: | Diseases/Neurodegeneration Neurobiology/Neuroscience Organisms/Drosophila Vision Vision/Photoreceptors Vision/Rhodopsin Vitamins and Cofactors/Carotenoid Vitamins and Cofactors/Retinoid |
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