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Lookup NU author(s): Dr Christophe Noel
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Retinoid X receptors (RXR) are members of the nuclear receptor superfamily of ligand-activated transcription factors that have been characterized in a wide variety of metazoan phyla. They act as heterodimer partners of other nuclear receptors, and in vertebrates also activate transcription as homodimers in the presence of a ligand, 9-cis retinoic acid. In order to test the hypothesis that retinoic acid signaling pathways involving RXRs are present in the Lophotrochozoa, we have sought to isolate conserved members of this family from the platyhelminth parasite Schistosoma mansoni and its intermediate host, the mollusk Biomphalaria glabrata. Here we report that an RXR ortholog from B. glabrata (BgRXR) is better conserved, compared with mouse RXRα, both in the DNA-binding domain (89% identity) and in the ligand-binding domain (LBD) (81% identity), than are arthropod homologs. In EMSA, BgRXR binds to the direct repeat response element DR1 as a homodimer or as a heterodimer with mammalian RARα, LXR, FXR or PPARα. When transfected alone into mammalian cell lines, BgRXR transactivated transcription of a reporter gene from the Apo-A1 promoter in the presence of 9-cis retinoic acid or DHA. Constructs with the Gal4 DNA binding domain fused to the hinge and LBDs of BgRXR were used to show that ligand-dependent activation of transcription by BgRXR required its intact AF-2 activation domain, and that the LBD can form homodimers. Finally, the binding of 9-cis retinoic acid preferentially protected the LBD of BgRXR from degradation by trypsin in a proteolysis protection assay. Our results show that BgRXR binds and is activated by retinoids and suggest that retinoid signaling pathways are conserved in the Lophotrochozoa. The nucleotide sequence reported in this paper has been submitted to the GenBank/EBI Data Bank with accession no. AY048663. © 2005 Society for Endocrinology.
Author(s): Bouton D, Escriva H, de Mendonca RL, Glineur C, Bertin B, Noel C, Robinson-Rechavi M, de Groot A, Cornette J, Laudet V, Pierce RJ
Publication type: Article
Publication status: Published
Journal: Journal of Molecular Endocrinology
Year: 2005
Volume: 34
Issue: 2
Pages: 567-582
Print publication date: 01/04/2005
ISSN (print): 0952-5041
ISSN (electronic): 1479-6813
Publisher: Society for Endocrinology
URL: http://dx.doi.org/10.1677/jme.1.01766
DOI: 10.1677/jme.1.01766
PubMed id: 15821117
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