RRC ID 54141
Author Okamoto N, Viswanatha R, Bittar R, Li Z, Haga-Yamanaka S, Perrimon N, Yamanaka N.
Title A Membrane Transporter Is Required for Steroid Hormone Uptake in Drosophila.
Journal Dev Cell
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.
Volume 47(3)
Pages 294-305.e7
Published 2018-11-5
DOI 10.1016/j.devcel.2018.09.012
PII S1534-5807(18)30741-X
PMID 30293839
PMC PMC6219898
MeSH 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
IF 10.092
Times Cited 14
Resource
Drosophila 7571R-1 HMJ24090 pBFv-U6.2 pBFv-U6.2B