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Properties of ecdysteroid receptors from diverse insect species in a heterologous cell culture system: a basis for screening novel insecticidal candidates

(2009) FEBS JOURNAL. 276(11). p.3087-3098
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Abstract
Insect development is driven by the action of ecdysteroids on morphogenetic processes. The classic ecdysteroid receptor is a protein heterodimer composed of two nuclear receptors, the ecdysone receptor (EcR) and Ultraspiracle (USP), the insect ortholog of retinoid X receptor. The functional properties of EcR and USP vary among insect species, and provide a basis for identifying novel and species-specific insecticidal candidates that disrupt this receptor's normal activity. A heterologous mammalian cell culture assay was used to assess the transcriptional activity of the heterodimeric ecdysteroid receptor from species representing two major insect orders: the fruit fly, Drosophila melanogaster (Diptera), and the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera). Several nonsteroidal agonists evoked a strong response with the L. decemlineata heterodimer that was consistent with biochemical and in vivo evidence, whereas the D. melanogaster receptor's response was comparatively modest. Conversely, the phytoecdysteroid muristerone A was more potent with the D. melanogaster heterodimer. The additional presence of juvenile hormone III potentiated the inductive activity of muristerone A in the receptors from both species, but juvenile hormone III was unable to potentiate the inductive activity of the diacylhydrazine methoxyfenozide (RH2485) in the receptor of either species. The effects of USP on ecdysteroid-regulated transcriptional activity also varied between the two species. When it was tested with D. melanogaster EcR isoforms, basal activity was lower and ligand-dependent activity was higher with L. decemlineata USP than with D. melanogaster USP. Generally, the species-based differences validate the use of the cell culture assay screen for novel agonists and potentiators as species-targeted insecticidal candidates.
Keywords
Drosophila, cell culture, insecticide, juvenile hormone, nonsteroidal agonist, COLORADO-POTATO-BEETLE, QUANTITATIVE STRUCTURE-ACTIVITY, DROSOPHILA ECDYSONE RECEPTOR, LIGAND-BINDING POCKET, RETINOID-X-RECEPTOR, LEPTINOTARSA-DECEMLINEATA, DIFFERENTIAL CONTROL, GROWTH-REGULATORS, RESPONSE ELEMENT, MAMMALIAN-CELLS

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Citation

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MLA
Beatty, Joshua M et al. “Properties of Ecdysteroid Receptors from Diverse Insect Species in a Heterologous Cell Culture System: a Basis for Screening Novel Insecticidal Candidates.” FEBS JOURNAL 276.11 (2009): 3087–3098. Print.
APA
Beatty, J. M., Smagghe, G., Ogura, T., Nakagawa, Y., Spindler-Barth, M., & Henrich, V. C. (2009). Properties of ecdysteroid receptors from diverse insect species in a heterologous cell culture system: a basis for screening novel insecticidal candidates. FEBS JOURNAL, 276(11), 3087–3098.
Chicago author-date
Beatty, Joshua M, Guy Smagghe, Takehiko Ogura, Yoshiaki Nakagawa, Margarethe Spindler-Barth, and Vincent C Henrich. 2009. “Properties of Ecdysteroid Receptors from Diverse Insect Species in a Heterologous Cell Culture System: a Basis for Screening Novel Insecticidal Candidates.” Febs Journal 276 (11): 3087–3098.
Chicago author-date (all authors)
Beatty, Joshua M, Guy Smagghe, Takehiko Ogura, Yoshiaki Nakagawa, Margarethe Spindler-Barth, and Vincent C Henrich. 2009. “Properties of Ecdysteroid Receptors from Diverse Insect Species in a Heterologous Cell Culture System: a Basis for Screening Novel Insecticidal Candidates.” Febs Journal 276 (11): 3087–3098.
Vancouver
1.
Beatty JM, Smagghe G, Ogura T, Nakagawa Y, Spindler-Barth M, Henrich VC. Properties of ecdysteroid receptors from diverse insect species in a heterologous cell culture system: a basis for screening novel insecticidal candidates. FEBS JOURNAL. 2009;276(11):3087–98.
IEEE
[1]
J. M. Beatty, G. Smagghe, T. Ogura, Y. Nakagawa, M. Spindler-Barth, and V. C. Henrich, “Properties of ecdysteroid receptors from diverse insect species in a heterologous cell culture system: a basis for screening novel insecticidal candidates,” FEBS JOURNAL, vol. 276, no. 11, pp. 3087–3098, 2009.
@article{681493,
  abstract     = {Insect development is driven by the action of ecdysteroids on morphogenetic processes. The classic ecdysteroid receptor is a protein heterodimer composed of two nuclear receptors, the ecdysone receptor (EcR) and Ultraspiracle (USP), the insect ortholog of retinoid X receptor. The functional properties of EcR and USP vary among insect species, and provide a basis for identifying novel and species-specific insecticidal candidates that disrupt this receptor's normal activity. A heterologous mammalian cell culture assay was used to assess the transcriptional activity of the heterodimeric ecdysteroid receptor from species representing two major insect orders: the fruit fly, Drosophila melanogaster (Diptera), and the Colorado potato beetle, Leptinotarsa decemlineata (Coleoptera). Several nonsteroidal agonists evoked a strong response with the L. decemlineata heterodimer that was consistent with biochemical and in vivo evidence, whereas the D. melanogaster receptor's response was comparatively modest. Conversely, the phytoecdysteroid muristerone A was more potent with the D. melanogaster heterodimer. The additional presence of juvenile hormone III potentiated the inductive activity of muristerone A in the receptors from both species, but juvenile hormone III was unable to potentiate the inductive activity of the diacylhydrazine methoxyfenozide (RH2485) in the receptor of either species. The effects of USP on ecdysteroid-regulated transcriptional activity also varied between the two species. When it was tested with D. melanogaster EcR isoforms, basal activity was lower and ligand-dependent activity was higher with L. decemlineata USP than with D. melanogaster USP. Generally, the species-based differences validate the use of the cell culture assay screen for novel agonists and potentiators as species-targeted insecticidal candidates.},
  author       = {Beatty, Joshua M and Smagghe, Guy and Ogura, Takehiko and Nakagawa, Yoshiaki and Spindler-Barth, Margarethe and Henrich, Vincent C},
  issn         = {1742-464X},
  journal      = {FEBS JOURNAL},
  keywords     = {Drosophila,cell culture,insecticide,juvenile hormone,nonsteroidal agonist,COLORADO-POTATO-BEETLE,QUANTITATIVE STRUCTURE-ACTIVITY,DROSOPHILA ECDYSONE RECEPTOR,LIGAND-BINDING POCKET,RETINOID-X-RECEPTOR,LEPTINOTARSA-DECEMLINEATA,DIFFERENTIAL CONTROL,GROWTH-REGULATORS,RESPONSE ELEMENT,MAMMALIAN-CELLS},
  language     = {eng},
  number       = {11},
  pages        = {3087--3098},
  title        = {Properties of ecdysteroid receptors from diverse insect species in a heterologous cell culture system: a basis for screening novel insecticidal candidates},
  url          = {http://dx.doi.org/10.1111/j.1742-4658.2009.07026.x},
  volume       = {276},
  year         = {2009},
}

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