The heterodimeric ecdysteroid receptor complex in the brown shrimp Crangon crangon EcR and RXR isoform characteristics and sensitivity towards the marine pollutant tributyltin

Yves Verhaegen, Koen Parmentier, Luc Swevers, Ellen Renders, Pierre Rougé, Wim De Coen, Kris Cooreman, Guy Smagghe

    Onderzoeksoutput: Bijdrage aan tijdschriftA1: Web of Science-artikel

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    Decapod crustaceans are characterized by multiple ecdysteroid receptor (EcR) and retinoid-X-receptor (RXR) isoforms, which likely exhibit variant dimerization and transactivation interactions. In the brown shrimp C. crangon we cloned C-terminally truncated CrcEcR and CrcRXR isoforms and isoforms exhibiting deletions within the hinge region. For the former, in silico modeling of the CrcEcR indicated that, where the conserved helices H10 and H11 of the ligand-binding domain (LBD) are missing, an alternative C-terminal a-helix repairs the ligand-binding pocket (LBP). The truncated CrcRXR isoforms lack a major part of the LBD (H4-H12), thereby compromising ligand binding and dimerization. Through an in vitro ecdysteroid responsive reporter assay, we showed that these natural receptor variations do not impair receptor functioning but probably alter the receptor dimerization preferences. By the same in vitro assay, using full-length CrcEcR and CrcRXR, the effect of tributyltin (TBT) on ecdysteroid-induced transactivation was evaluated. The transactivation by 10nM PonA was reduced with 64% by 20 nM TBT. In silico modeling confirmed that TBT fits in the full-length CrcRXR-LBD. Furthermore, semi-quantitative PCR indicated altered expression of CrcEcR and CrcRXR isoforms after in vivo acute exposure to TBT, especially in the ovaries.
    TaalEngels
    TijdschriftGeneral and Comparative Endocrinology
    Volume172
    Exemplaarnummer1
    Pagina's (van-tot)158-69
    Aantal pagina's12
    DOI's
    StatusGepubliceerd - 2011

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