The Drosophila class B scavenger receptor NinaD-I is a cell surface receptor mediating carotenoid transport for visual chromophore synthesis

Biochemistry. 2006 Nov 14;45(45):13429-37. doi: 10.1021/bi060701u.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • CD36 Antigens / physiology*
  • Carotenoids / metabolism
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / metabolism
  • Intracellular Membranes / metabolism
  • Receptors, Immunologic / physiology*
  • alpha-Tocopherol / metabolism

Substances

  • CD36 Antigens
  • Drosophila Proteins
  • NinaD protein, Drosophila
  • Receptors, Immunologic
  • Carotenoids
  • alpha-Tocopherol