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A Membrane Transporter Is Required for Steroid Hormone Uptake in Drosophila.

Developmental cell | 2018

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.

Pubmed ID: 30293839 RIS Download

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Associated grants

  • Agency: NIH HHS, United States
    Id: P40 OD010949
  • Agency: NIH HHS, United States
    Id: P40 OD018537
  • Agency: NICHD NIH HHS, United States
    Id: R00 HD073239
  • Agency: NCRR NIH HHS, United States
    Id: R24 RR032668
  • Agency: Howard Hughes Medical Institute, United States

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Bloomington Drosophila Stock Center (tool)

RRID:SCR_006457

Collects, maintains and distributes Drosophila melanogaster strains for research. Emphasis is placed on genetic tools that are useful to a broad range of investigations. These include basic stocks of flies used in genetic analysis such as marker, balancer, mapping, and transposon-tagging strains; mutant alleles of identified genes, including a large set of transposable element insertion alleles; defined sets of deficiencies and a variety of other chromosomal aberrations; engineered lines for somatic and germline clonal analysis; GAL4 and UAS lines for targeted gene expression; enhancer trap and lacZ-reporter strains with defined expression patterns for marking tissues; and a collection of transposon-induced lethal mutations.

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Anti-GFP antibody (antibody)

RRID:AB_300798

This polyclonal targets GFP

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w[1118]; PBac{y[+mDint2] w[+mC]=20XUAS-IVS-GCaMP6m}VK00005 (organism)

RRID:BDSC_42750

Drosophila melanogaster with name w[1118]; PBac{y[+mDint2] w[+mC]=20XUAS-IVS-GCaMP6m}VK00005 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02880}attP2 (organism)

RRID:BDSC_44583

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02880}attP2 from BDSC.

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y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02972}attP2 (organism)

RRID:BDSC_50736

Drosophila melanogaster with name y[1] sc[*] v[1] sev[21]; P{y[+t7.7] v[+t1.8]=TRiP.HMS02972}attP2 from BDSC.

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w[1118]; P{w[+mC]=UAS-EcR-RNAi}104 (organism)

RRID:BDSC_9327

Drosophila melanogaster with name w[1118]; P{w[+mC]=UAS-EcR-RNAi}104 from BDSC.

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w[*]; P{w[+mC]=UAS-2xEGFP}AH2 (organism)

RRID:BDSC_6874

Drosophila melanogaster with name w[*]; P{w[+mC]=UAS-2xEGFP}AH2 from BDSC.

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y[1] w[*]; P{w[+mC]=tubP-GAL4}LL7/TM3, Sb[1] Ser[1] (organism)

RRID:BDSC_5138

Drosophila melanogaster with name y[1] w[*]; P{w[+mC]=tubP-GAL4}LL7/TM3, Sb[1] Ser[1] from BDSC.

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w[*]; P{w[+mC]=Sgs3-GFP}3 (organism)

RRID:BDSC_5885

Drosophila melanogaster with name w[*]; P{w[+mC]=Sgs3-GFP}3 from BDSC.

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w[*]; P{w[+mC]=EcRE.lacZ}SS3 (organism)

RRID:BDSC_4517

Drosophila melanogaster with name w[*]; P{w[+mC]=EcRE.lacZ}SS3 from BDSC.

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y[*] w[*]; P{w[+mC]=EcRE.lacZ}SS4 (organism)

RRID:BDSC_4516

Drosophila melanogaster with name y[*] w[*]; P{w[+mC]=EcRE.lacZ}SS4 from BDSC.

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w[*]; Kr[If-1]/CyO; P{w[+mW.hs]=GAL4-da.G32}UH1 (organism)

RRID:BDSC_55850

Drosophila melanogaster with name w[*]; Kr[If-1]/CyO; P{w[+mW.hs]=GAL4-da.G32}UH1 from BDSC.

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w[1118]; P{w[+mC]=Cg-GAL4.A}2 (organism)

RRID:BDSC_7011

Drosophila melanogaster with name w[1118]; P{w[+mC]=Cg-GAL4.A}2 from BDSC.

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w[*]; P{w[+mW.hs]=GAL4-arm.S}4a P{w[+mW.hs]=GAL4-arm.S}4b/TM3, Sb[1] Ser[1] (organism)

RRID:BDSC_1561

Drosophila melanogaster with name w[*]; P{w[+mW.hs]=GAL4-arm.S}4a P{w[+mW.hs]=GAL4-arm.S}4b/TM3, Sb[1] Ser[1] from BDSC.

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w[*]; P{w[+mW.hs]=GAL4-arm.S}11 (organism)

RRID:BDSC_1560

Drosophila melanogaster with name w[*]; P{w[+mW.hs]=GAL4-arm.S}11 from BDSC.

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y[1] w[*]; P{w[+mC]=Act5C-GAL4}17bFO1/TM6B, Tb[1] (organism)

RRID:BDSC_3954

Drosophila melanogaster with name y[1] w[*]; P{w[+mC]=Act5C-GAL4}17bFO1/TM6B, Tb[1] from BDSC.

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w[1118]; PBac{y[+mDint2] w[+mC]=20XUAS-IVS-GCaMP6m}VK00005 (organism)

RRID:BDSC_42750

Drosophila melanogaster with name w[1118]; PBac{y[+mDint2] w[+mC]=20XUAS-IVS-GCaMP6m}VK00005 from BDSC.

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