Dimerization, host-parasite communication and expression studies of an Echinococcus granulosus 2DBD nuclear receptor.

Abstract

Nuclear receptors (NRs) are ligand-modulated transcription factors that regulate various biological processes, such as metabolism, development and reproduction. Although NRs with two DNA-binding domains (2DBD) were identified in Schistosoma mansoni (Platyhelminth, Trematoda) more than fifteen years ago, these proteins have been poorly studied. 2DBD-NRs could become attractive therapeutic targets to combat parasitic diseases such as cystic echinococcosis since this type of protein is absent in vertebrate hosts. Cystic echinococcosis is a worldwide zoonosis caused by the larval stage of the parasitic platyhelminth Echinococcus granulosus (Cestoda) that generates an important public health problem and a significant economic loss. Recently, our research group identified four 2DBD-NRs in E. granulosus, named Eg2DBDα, Eg2DBDα.1 (an isoform of Eg2DBDα), Eg2DBDβ, and Eg2DBDγ. This work demonstrated that Eg2DBDα.1 forms homodimers through the E and F regions, whereas its interaction with EgRXRβa could not be detected. In addition, the stimulation of Eg2DBDα.1 homodimerization by intermediate host serum was shown, suggesting that at least one lipophilic molecule from bovine serum could bind to Eg2DBDα.1. Finally, Eg2DBDs expression studies in the protoscolex larval stage were performed, indicating that Eg2dbdγ is not expressed, whereas Eg2dbdα has the highest expression level followed by Eg2dbdβ and Eg2dbdα.1 in decreased order. Overall, these findings provide new insights into the mechanism of action of Eg2DBDα.1 and its potential role in host-parasite communication.