However, the RBPs required for Drosophila vision have not been identified. In addition, two genes ( ninaB and ninaD) function outside the retina for production of vitamin A ( Stephenson et al., 1983 Gu et al., 2004) and encode a β,β-carotene-15,15′-dioxgenase and a class B scavenger receptor, respectively ( von Lintig et al., 2001 Kiefer et al., 2002). One enzyme that functions in the transformation of the retinal to the chromophore is an oxidoreductase encoded by the neither inactivation nor afterpotential G ( ninaG) locus ( Sarfare et al., 2005). Nevertheless, the RBPs and enzymes necessary for conversion of free all- trans- to cis-retinal must exist, because dietary vitamin A is sufficient for production of the 11- cis-retinal. The all- trans-retinal is converted to cis-retinal in photoreceptor cells in a light-rather than an enzyme-dependent manner. In Drosophila, light does not cause the chromophore to release from the opsin. However, the specific roles of many RBPs are unresolved. In addition, some RBPs are thought to promote transfer of retinoids between cell types, whereas others are proposed to sequester retinoids to create concentration gradients that facilitate reactions that would otherwise be unfavorable ( Noy, 2000 Gonzalez-Fernandez, 2002). Retinoids must associate with RBPs, because they are hydrophobic. The critical role for this cycle is reflected by the severe retinal diseases resulting from mutations disrupting two retinal dehydrogenases and two retinoid-binding proteins (RBPs) (for review, see Thompson and Gal, 2003). The 11- cis- retinal is then returned to the rods and cones. A more rapid retinoid cycle leading to regeneration of the cone rhodopsins occurs in the Müller cells ( Mata et al., 2002). Regeneration of the cis-retinal in mammalian rods involves release of the all- trans-retinal from the opsin and formation of vitamin A, which is transported to the retinal pigment epithelium (RPE) and converted into 11- cis-retinal. Light results in a cis-to- trans isomerization of the chromophore, and this transformation represents the only light-driven step during phototransduction. The retinoids required for Drosophila and mammalian phototransduction (3-hydroxy-11- cis-retinal and 11- cis-retinal, respectively) ( Wald, 1968 Vogt and Kirschfeld, 1984 Tanimura et al., 1986) bind to the opsin to form rhodopsin (Rh). In contrast to mammals, the fruit fly, Drosophila melanogaster, appears to require retinoids exclusively in the retina ( Harris et al., 1977). Defects in retinoid levels are associated with many forms of cancer as well as neurodegenerative diseases including retinitis pigmentosa, Parkinson's disease, and Huntington's disease (for review, see Simoni and Tolomeo, 2001 Thompson and Gal, 2003 Mey and McCaffery, 2004). Vitamin A (all- trans-retinol) and other retinoids are critical for processes ranging from development to visual pigment regeneration, neuronal plasticity, and cell proliferation (for review, see Simoni and Tolomeo, 2001 Thompson and Gal, 2003 Mey and McCaffery, 2004). Moreover, our data implicate Drosophila retinal pigment cells as functioning in the conversion of dietary all- trans-retinol to 11- cis-retinal and suggest that these cells are the closest invertebrate equivalent to the RPE. These results represent the first genetic evidence for a role for the retinal pigment cells in the visual response. We demonstrate that PINTA functions subsequent to the production of vitamin A and is expressed and required in the retinal pigment cells. In a genetic screen for mutations that affect the biosynthesis of rhodopsin, we identified a novel CRAL-TRIO domain protein, prolonged depolarization afterpotential is not apparent (PINTA), which binds to all- trans-retinol. Here, we establish the Drosophila visual system as a genetic model for characterizing retinoid-binding proteins. Although this cycle has been studied extensively in mammals, many questions remain, including the specific roles of retinoid-binding proteins. In mammals, the all- trans-retinal is converted to vitamin A (all- trans-retinol) and is transported to the retinal pigment epithelium (RPE), where along with dietary vitamin A, it is converted into 11- cis-retinal. 11- cis-retinal binds to opsin and undergoes a light-driven isomerization to all- trans-retinal. Retinoids participate in many essential processes including the initial event in photoreception.
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