Cited by 144Drug Transport and Resistance MechanismsEstrogen and related hormone effectsNeurobiology and Insect Physiology Research

A Membrane Transporter Is Required for Steroid Hormone Uptake in Drosophila

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Okamoto, Naoki, Viswanatha, Raghuvir, Bittar, Riyan, Li, Zhongchi, Haga-Yamanaka, Sachiko, Perrimon, Norbert, Yamanaka, Naoki·2018·Developmental 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.

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  1. Urry LA, Cain ML, Wasserman SA, Minorsky PV, and Reece JB (2017). Campbell Biology, 11th edition (New York: Pearson).

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Authors
Okamoto, N., Viswanatha, R., Bittar, R., Li, Z., Haga-Yamanaka, S., Perrimon, N., & Yamanaka, N.
Affiliations
  • University of California, Riverside (US)
  • Harvard University (US)
  • Howard Hughes Medical Institute (US)
Corresponding author
Yamanaka, Naoki
Venue
Developmental Cell
Publisher
Elsevier BV
Published
2018-11
Volume
47
Issue
3
Pages
294-305.e7
ISSN
1534-5807 (ISSN-L)
OpenAlex
W2894774020
Cited by
144
References
77
Citations by year
2026: 14 · 2025: 27 · 2024: 15 · 2023: 16 · 2022: 23 · 2021: 21 · 2020: 17 · 2019: 7 · 2018: 4
FWCI
4.59
Type
journal article
Language
en
Open access
Locations
  • Developmental Cell (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • Bloomington Drosophila Stock Center
  • NIH (P40 OD018537, R24 RR032668, P40 OD010949, R00 HD073239)
  • National Institute of Genetics
  • Harvard Medical School
  • Developmental Studies Hybridoma Bank
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development
  • The University of Iowa
  • Japan Society for the Promotion of Science
  • Naito Foundation
  • W.M. Keck Foundation
  • Pew Charitable Trusts
  • Howard Hughes Medical Institute
Topics
  • Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
Keywords
membrane transporters, steroid hormone transport, organic anion transporting polypeptides, solute carrier transporters, ecdysone receptor, ecdysone signaling, Drosophila, cell-autonomous signaling, nuclear receptors
MeSH terms
Animals, Drosophila melanogaster, Ecdysone, Receptors, Steroid, Steroids, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Membrane Transport Proteins, Drosophila Proteins

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