A Membrane Transporter Is Required for Steroid Hormone Uptake in Drosophila

Dev Cell. 2018 Nov 5;47(3):294-305.e7. doi: 10.1016/j.devcel.2018.09.012. Epub 2018 Oct 4.

Abstract

Steroid hormones are a group of lipophilic hormones that are believed to enter cells by simple diffusion to regulate diverse physiological processes through intracellular nuclear receptors. Here, we challenge this model in Drosophila by demonstrating that Ecdysone Importer (EcI), a membrane transporter identified from two independent genetic screens, is involved in cellular uptake of the steroid hormone ecdysone. EcI encodes an organic anion transporting polypeptide of the evolutionarily conserved solute carrier organic anion superfamily. In vivo, EcI loss of function causes phenotypes indistinguishable from ecdysone- or ecdysone receptor (EcR)-deficient animals, and EcI knockdown inhibits cellular uptake of ecdysone. Furthermore, EcI regulates ecdysone signaling in a cell-autonomous manner and is both necessary and sufficient for inducing ecdysone-dependent gene expression in culture cells expressing EcR. Altogether, our results challenge the simple diffusion model for cellular uptake of ecdysone and may have wide implications for basic and medical aspects of steroid hormone studies.

Keywords: OATP; SLCO; ecdysone; membrane transporter; nuclear receptor; steroid hormone.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / metabolism
  • Ecdysone / metabolism*
  • Membrane Transport Proteins / metabolism
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Receptors, Steroid / metabolism*
  • Signal Transduction / physiology
  • Steroids / metabolism

Substances

  • Drosophila Proteins
  • Membrane Transport Proteins
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Steroid
  • Steroids
  • ecdysone receptor
  • Ecdysone