The ligand-binding domains of the three RXR-USP nuclear receptor types support distinct tissue and ligand specific hormonal responses in transgenic Drosophila.
In insects, 20-hydroxyecdysone acts by binding on a heterodimer constituted by the ecdysone receptor (EcR) and Ultraspiracle (USP), the homolog to the vertebrate retinoid X receptor (RXR). Two types of USP have been characterized based on their structure and function, Mecopterida USP (Diptera/Lepidoptera USP), in particular the fruitfly Drosophila melanogaster USP (DmUSP) and non Mecopterida USP, exemplified by the beetle Tribolium castaneum USP (TcUSP) both showing structural differences from the vertebrate RXR. Here, by combining in vivo and organ culture observations in Drosophila transgenic animals, we show that ectopic expression of GAL4-DmUSP, GAL4-TcUSP or GAL4-HsRXR results in tissue- and ligand-dependent activities. In parallel, we show that neither juvenile hormone (JH) nor the related methyl farnesoate has an effect on GAL4-USP activation although JH induces the expression of a factor inhibiting the receptor transcriptional activity in the presence of EcR or RXR agonists. This study suggests that not only is USP important for hormonal regulation, via heterodimer formation, but that tissue-specific expression of cofactors may represent a higher level of control of this regulation. This in vivo approach should lead to a better understanding of the modes of action of USP and the identification of transcriptional cofactors essential for its function.
Beck
Yannick
Y
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Département de Biologie et de Génomique Structurales, Illkirch, France.
Delaporte
Claude
C
Moras
Dino
D
Richards
Geoff
G
Billas
Isabelle M L
IM
D000818:Animals; D030801:Animals, Genetically Modified; D001665:Binding Sites; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019281:Dimerization; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000235:genetics* / Q000378:metabolism*; D004441:Ecdysterone / Q000494:pharmacology; D008024:Ligands; D008954:Models, Biological; D017434:Protein Structure, Tertiary; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D011987:Receptors, Steroid / Q000378:metabolism; D047488:Retinoid X Receptors / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014231:Tribolium / Q000378:metabolism
D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D011987:Receptors, Steroid; D047488:Retinoid X Receptors; D014157:Transcription Factors; C066030:USP protein, Drosophila; C055469:ecdysone receptor; D004441:Ecdysterone