title: A functionally conserved member of the FTZ-F1 nuclear receptor family from Schistosoma mansoni.
abstract: The fushi tarazu factor 1 (FTZ-F1) nuclear receptor subfamily comprises orphan receptors with crucial roles in development and sexual differentiation in vertebrates and invertebrates. We describe the structure and functional properties of an FTZ-F1 from the platyhelminth parasite of humans, Schistosoma mansoni, the first receptor from this family to be characterized in a Lophotrochozoan. It contains a well conserved DNA-binding domain (55-63% identity to other family members) and a poorly conserved ligand-binding domain (20% identity to that of zebrafish FF1a). However, both the ligand domain signature sequence and the activation function 2-activation domain (AF2-AD) are perfectly conserved. Phylogenetic analysis confirmed that SmFTZ-F1 is a member of nuclear receptor subfamily 5, but that it clustered with the Drosophila receptor DHR39 and has consequently been named NR5B1. The gene showed a complex structure with 10 exons and an overall size of 18.4 kb. Two major transcripts were detected, involving alternative promoter usage and splicing of the two 5' exons, but which encoded identical proteins. SmFTZ-F1 mRNA is expressed at all life-cycle stages with the highest amounts in the larval forms (miracidia, sporocysts and cercariae). However, expression of the protein showed a different pattern; low in miracidia and higher in adult male worms. The protein bound the same monomeric response element as mammalian SF-1 (SF-1 response element, SFRE) and competition experiments with mutant SFREs showed that its specificity was identical. Moreover, SmFTZ-F1 transactivated reporter gene transcription from SFRE similarly to SF-1. This functional conservation argues for a conserved biological role of the FTZ-F1 nuclear receptor family throughout the metazoa.
authors.affiliation: INSERM U 547, Institut Pasteur, Lille, France; CNRS UMR 49, Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: De Mendonça
authors.forename: Didier
authors.initials: D
authors.lastname: Bouton
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bertin
authors.forename: Hector
authors.initials: H
authors.lastname: Escriva
authors.forename: Christophe
authors.initials: C
authors.lastname: Noël
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Vanacker
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Cornette
authors.forename: Vincent
authors.initials: V
authors.lastname: Laudet
authors.forename: Raymond J
authors.initials: RJ
authors.lastname: Pierce
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D015723:Gene Library; D017930:Genes, Reporter; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry*; D010802:Phylogeny; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012550:Schistosoma mansoni / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D014157:Transcription Factors / Q000737:chemistry*; D015533:Transcriptional Activation; D014162:Transfection; D029961:Zebrafish Proteins
chemical_list: D018076:DNA, Complementary; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D029961:Zebrafish Proteins; C478921:nr5a1a protein, zebrafish; D004247:DNA