The Drosophila Class B Scavenger Receptor NinaD-I Is a Cell Surface Receptor Mediating Carotenoid Transport for Visual Chromophore Synthesis
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文摘
The blind Drosophila mutant ninaD lacks the visual chromophore. Genetic evidence that themolecular basis is a defect in carotenoid uptake which causes vitamin A deficiency exists. The ninaDgene encodes a scavenger receptor that is significantly homologous in sequence with the mammalianscavenger receptors SR-BI (scavenger receptor class B type I) and CD36 (cluster determinant 36), yetNinaD has not been characterized in functional detail. Therefore, we established a Drosophila S2 cellculture system for biochemically characterizing the ninaD gene products. We show that the two splicevariant isoforms encoded by ninaD exhibit different subcellular localizations. NinaD-I, the long proteinvariant, is localized at the plasma membrane, whereas the short variant, NinaD-II, is localized at intracellularmembranes. Only NinaD-I could mediate the cellular uptake of carotenoids from micelles in this cellculture system. Carotenoid uptake was concentration-dependent and saturable. By in vivo analyses ofdifferent mutant and transgenic fly strains, we provide evidence of an essential role of NinaD-I in theabsorption of dietary carotenoids to support visual chromophore synthesis. Moreover, our analyses suggesta role of NinaD-I in tocopherol metabolism. Even though Drosophila is a sterol auxotroph, we found noevidence of a contribution of NinaD-I to the uptake of these compounds. Together, our study establishesan evolutionarily conserved connection between class B scavenger receptors and the numerous functionsof fat soluble vitamins in animal physiology.

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