Role of a novel nuclear receptor fushi tarazu factor 1 (SmFTZ-F1alpha) in the biology of Schistosoma mansoni
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Schistosoma mansoni is a major etiologic agent of schistosomiasis, a disease of world health importance. A better understanding of the schistosome female reproductive development will provide new approaches in controlling worm fecundity and thus disease transmission and pathology. Previous studies on schistosome female-specific genes suggested that schistosome nuclear receptors would be involved in stage-specific gene regulation. The identification of S. mansoni retinoid X receptor, SmRXR, and its interaction with p14 promoter region further supported the involvement of NRs in schistosome gender-specific gene regulation. Further studies identified a family of S. mansoni nuclear receptors. The focus of this study is on one S. mansoni nuclear receptor, SmFTZ-F1α. SmFTZ-F1α is the second FTZ-F1-like protein identified in S. mansoni . Encoded by Smftz-f1α gene, which is located on Chromosome 2 and composed of 15 exons, SmFTZ-F1α is a large protein of 1892 aa. By phylogenetic analysis, SmFTZ-F1α is more closely related to Drosophila FTZ-F1α (DmFTZ-F1α), the homologue of all mammalian FTZ-F1-like proteins, while the first identified schistosome FTZ-F1 (SmFTZ-F1) is grouped with DHR39, another FTZ-F1-like protein in Drosophila . By western blot analysis, a native schistosome protein with a predicted size of SmFTZ-F1α (206 kDa) and a smaller protein (120 kDa) were identified in an adult male worm extract. Smftz-f1α was shown by RT-PCR to be expressed throughout the entire schistosome life cycle with the highest level in the egg stage. SmFTZ-F1α possesses a conserved DNA binding domain (DBD, C domain) that recognized FTZ-F1/steroidogenic factor response element (SFRE, PyCAAGGPyCPu), the consensus sequence for FTZ-F1-like proteins. However, the optimal binding element for SmFTZ-F1α is TNPuAGGTCPu. The C domain strongly bound to a putative hormone response element (TTAAGGTCA) found in the upstream region of p14 . In yeast, full-length SmFTZ-F1α transactivated reporter genes via an activation function (AF)-1 motif in the AB domain. A second autonomous activation motif (named AF-3) was identified in the hinge region (aa 982 to aa 1110). The SmFTZ-F1α transcript and protein were widely distributed in tissues of adult worms, but were not found in the female vitelline cells. In gonads of the male and female schistosomes, a distinct SmFTZ-F1α protein signal was detected by immunofluorescent staining. Taken together, the data suggest multiple roles of SmFTZ-F1α in schistosome biology, especially in embryogenesis and reproductive system development.