title: The Drosophila class B scavenger receptor NinaD-I is a cell surface receptor mediating carotenoid transport for visual chromophore synthesis.
abstract: The blind Drosophila mutant ninaD lacks the visual chromophore. Genetic evidence that the molecular basis is a defect in carotenoid uptake which causes vitamin A deficiency exists. The ninaD gene encodes a scavenger receptor that is significantly homologous in sequence with the mammalian scavenger receptors SR-BI (scavenger receptor class B type I) and CD36 (cluster determinant 36), yet NinaD has not been characterized in functional detail. Therefore, we established a Drosophila S2 cell culture system for biochemically characterizing the ninaD gene products. We show that the two splice variant isoforms encoded by ninaD exhibit different subcellular localizations. NinaD-I, the long protein variant, is localized at the plasma membrane, whereas the short variant, NinaD-II, is localized at intracellular membranes. Only NinaD-I could mediate the cellular uptake of carotenoids from micelles in this cell culture system. Carotenoid uptake was concentration-dependent and saturable. By in vivo analyses of different mutant and transgenic fly strains, we provide evidence of an essential role of NinaD-I in the absorption of dietary carotenoids to support visual chromophore synthesis. Moreover, our analyses suggest a role of NinaD-I in tocopherol metabolism. Even though Drosophila is a sterol auxotroph, we found no evidence of a contribution of NinaD-I to the uptake of these compounds. Together, our study establishes an evolutionarily conserved connection between class B scavenger receptors and the numerous functions of fat soluble vitamins in animal physiology.
authors.affiliation: Institute of Biology I, University of Freiburg, Hauptstrasse 1, D-79104 Freiburg im Breisgau, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Voolstra
authors.forename: Cornelia
authors.initials: C
authors.lastname: Kiefer
authors.forename: Martin
authors.initials: M
authors.lastname: Hoehne
authors.forename: Ralf
authors.initials: R
authors.lastname: Welsch
authors.forename: Klaus
authors.initials: K
authors.lastname: Vogt
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D018955:CD36 Antigens / Q000502:physiology*; D002338:Carotenoids / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D029721:Drosophila Proteins / Q000502:physiology*; D004331:Drosophila melanogaster / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D011971:Receptors, Immunologic / Q000502:physiology*; D024502:alpha-Tocopherol / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; D029721:Drosophila Proteins; C465435:NinaD protein, Drosophila; D011971:Receptors, Immunologic; D002338:Carotenoids; D024502:alpha-Tocopherol