title: NinaB is essential for Drosophila vision but induces retinal degeneration in opsin-deficient photoreceptors.
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 beta-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.
authors.affiliation: Institut für Biologie I, Neurobiologie und Tiephysiologie, Albert-Ludwigs Universität, D-79102 Freiburg, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Voolstra
authors.forename: Vitus
authors.initials: V
authors.lastname: Oberhauser
authors.forename: Emerich
authors.initials: E
authors.lastname: Sumser
authors.forename: Nina E
authors.initials: NE
authors.lastname: Meyer
authors.forename: Michael E
authors.initials: ME
authors.lastname: Maguire
authors.forename: Armin
authors.initials: A
authors.lastname: Huber
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000378:metabolism; D054910:Compound Eye, Arthropod / Q000254:growth & development; D004330:Drosophila / Q000166:cytology / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005123:Eye / Q000378:metabolism; D005786:Gene Expression Regulation; D007814:Larva / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D055355:Opsins / Q000172:deficiency* / Q000235:genetics; D010786:Photoreceptor Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012162:Retinal Degeneration / Q000378:metabolism*; D012168:Retinal Pigments / Q000096:biosynthesis; D012172:Retinaldehyde / Q000494:pharmacology; D012177:Retinol-Binding Proteins / Q000378:metabolism; D014785:Vision, Ocular; D024341:Xanthophylls / Q000378:metabolism; D065146:Zeaxanthins; D050559:beta-Carotene 15,15'-Monooxygenase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D055355:Opsins; C507946:PINTA protein, Drosophila; D012168:Retinal Pigments; D012177:Retinol-Binding Proteins; D024341:Xanthophylls; D065146:Zeaxanthins; C493360:ninaB protein, Drosophila; D002338:Carotenoids; D050559:beta-Carotene 15,15'-Monooxygenase; D012172:Retinaldehyde