Abstract:We previously reported (Sarfare, S., Ahmad, S. T., Joyce, M. V., Boggess, B., and O'Tousa, J. E. (2005) J. Biol. Chem. 280, 11895-11901) that the Drosophila ninaG gene encodes an oxidoreductase involved in the biosynthesis of the (3S)-3-hydroxyretinal serving as chromophore for Rh1 rhodopsin and that ninaG mutant flies expressing Rh4 as the major opsin accumulate large amounts of a different retinoid. Here, we show that this unknown retinoid is 11-cis-3-hydroxyretinol. Reversed phase high performance liquid ch… Show more
“…The all-trans-retinal is then metabolized into vitamin A and transferred to the retinal pigment cells, where it is converted into the chromophore, through a process involving the PINTA retinoid binding protein (Wang and Montell, 2005). The NINAG oxidoreductase also participates in the production of the chromophore, in a step subsequent to the formation of vitamin A (Sarfare et al, 2005; Ahmad et al, 2006), although it remains to be determined whether it functions in the retinal pigment cells or in photoreceptor cells.…”
Dietary carotenoids are precursors for the production of retinoids, which participate in many essential processes, including the formation of the photopigment rhodopsin. Despite the importance of conversion of carotenoids to vitamin A (all-trans-retinol), many questions remain concerning the mechanisms that promote this process, including the uptake of carotenoids. We use the Drosophila visual system as a genetic model to study retinoid formation from β-carotene. In a screen for mutations that affect the biosynthesis of rhodopsin, we identified a class B scavenger receptor, SANTA MARIA. We demonstrate that SANTA MARIA functions upstream of vitamin A formation in neurons and glia, which are outside of the retina. The protein is coexpressed and functionally coupled with the β, β-carotene-15, 15′-monooxygenase, NINAB, which converts β-carotene to all-trans-retinal. Another class B scavenger receptor, NINAD, functions upstream of SANTA MARIA in the uptake of carotenoids, enabling us to propose a pathway involving multiple extraretinal cell types and proteins essential for the formation of rhodopsin.
“…The all-trans-retinal is then metabolized into vitamin A and transferred to the retinal pigment cells, where it is converted into the chromophore, through a process involving the PINTA retinoid binding protein (Wang and Montell, 2005). The NINAG oxidoreductase also participates in the production of the chromophore, in a step subsequent to the formation of vitamin A (Sarfare et al, 2005; Ahmad et al, 2006), although it remains to be determined whether it functions in the retinal pigment cells or in photoreceptor cells.…”
Dietary carotenoids are precursors for the production of retinoids, which participate in many essential processes, including the formation of the photopigment rhodopsin. Despite the importance of conversion of carotenoids to vitamin A (all-trans-retinol), many questions remain concerning the mechanisms that promote this process, including the uptake of carotenoids. We use the Drosophila visual system as a genetic model to study retinoid formation from β-carotene. In a screen for mutations that affect the biosynthesis of rhodopsin, we identified a class B scavenger receptor, SANTA MARIA. We demonstrate that SANTA MARIA functions upstream of vitamin A formation in neurons and glia, which are outside of the retina. The protein is coexpressed and functionally coupled with the β, β-carotene-15, 15′-monooxygenase, NINAB, which converts β-carotene to all-trans-retinal. Another class B scavenger receptor, NINAD, functions upstream of SANTA MARIA in the uptake of carotenoids, enabling us to propose a pathway involving multiple extraretinal cell types and proteins essential for the formation of rhodopsin.
“…The chromophore is transported to the photoreceptor cells where it binds to the opsin resulting in the generation of rhodopsin pigment epithelium (RPE) [72], it appears that Drosophila retinal pigment cells are the closest functional equivalent to the RPE. The ninaG gene encodes an oxidoreductase, which is proposed to act in the conversion of (3R)-3hydroxyretinol to the 3S enantiomer in the compound eye [82,83]. However, it is not known whether ninaG functions in the retinal pigment cells or in photoreceptor cells.…”
Drosophila visual transduction is the fastest known G-protein-coupled signaling cascade and has therefore served as a genetically tractable animal model for characterizing rapid responses to sensory stimulation. Mutations in over 30 genes have been identified, which affect activation, adaptation, or termination of the photoresponse. Based on analyses of these genes, a model for phototransduction has emerged, which involves phosphoinoside signaling and culminates with opening of the TRP and TRPL cation channels. Many of the proteins that function in phototransduction are coupled to the PDZ containing scaffold protein INAD and form a supramolecular signaling complex, the signalplex. Arrestin, TRPL, and Gα q undergo dynamic light-dependent trafficking, and these movements function in long-term adaptation. Other proteins play important roles either in the formation or maturation of rhodopsin, or in regeneration of phosphatidylinositol 4,5-bisphosphate (PIP 2 ), which is required for the photoresponse. Mutation of nearly any gene that functions in the photoresponse results in retinal degeneration. The underlying bases of photoreceptor cell death are diverse and involve mechanisms such as excessive endocytosis of rhodopsin due to stable rhodopsin/arrestin complexes and abnormally low or high levels of Ca 2+ . Drosophila visual transduction appears to have particular relevance to the cascade in the intrinsically photosensitive retinal ganglion cells in mammals, as the photoresponse in these latter cells appears to operate through a remarkably similar mechanism.
“…RDGC catalyzes the dephosphorylation of rhodopsin, 41,42 whereas CaMKII is involved in the phosphorylation of arrestin 2 (Arr2), 43,44 the major visual arrestin critical for the inactivation of activated rhodopsin. 45 Eye-PKC is a conventional PKC 46 activated by both 69 and santa maria (scavenger receptor acting in neural tissue and majority of rhodopsin is absent). 70 The stability of Drosophila Rh1 rhodopsin is dependent on its incorporation of the retinal chromophore: 71 flies defective in proteins that control the uptake or processing of vitamin A, contain a reduced level of Rh1.…”
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