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: Olaf Voolstra, Vitus Oberhauser, Emerich Sumser, Nina E Meyer, Michael E Maguire, Armin Huber, Johannes von Lintig
• Journal: The Journal of biological chemistry (J Biol Chem) Vol. 285 Issue 3 Pg. 2130-9 (Jan 15 2010) ISSN: 1083-351X [Electronic] United States
• PMID: 19889630 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Drosophila Proteins
• Opsins
• PINTA protein, Drosophila
• Retinal Pigments
• Retinol-Binding Proteins
• Xanthophylls
• Zeaxanthins
• ninaB protein, Drosophila
• Carotenoids
• beta-Carotene 15,15'-Monooxygenase
• Retinaldehyde

Topics

• Animals
• Carotenoids (metabolism)
• Compound Eye, Arthropod (growth & development)
• Drosophila (cytology, growth & development, metabolism, physiology)
• Drosophila Proteins (chemistry, genetics, metabolism)
• Eye (metabolism)
• Gene Expression Regulation
• Larva (metabolism, physiology)
• Mutation
• Opsins (deficiency, genetics)
• Photoreceptor Cells (drug effects, metabolism, pathology)
• Retinal Degeneration (metabolism)
• Retinal Pigments (biosynthesis)
• Retinaldehyde (pharmacology)
• Retinol-Binding Proteins (metabolism)
• Vision, Ocular
• Xanthophylls (metabolism)
• Zeaxanthins
• beta-Carotene 15,15'-Monooxygenase (chemistry, genetics, metabolism)