Deorphanizing G protein-coupled receptors in Schistosoma mansoni utilizing the MALAR yeast two-hybrid system

Schedule : Back to Dr Oliver Weth

Poster

Deorphanizing G protein-coupled receptors in Schistosoma mansoni utilizing the MALAR yeast two-hybrid system

Authors

O Weth²; Z Lu⁴; S Hahnel¹; J li³; C G Grevelding²;
¹ Department of Molecular Biosciences, Northwestern University, United States; ² Institute of Parasitology, BFS, Justus-Liebig-University Giessen, Germany; ³ Laboratory of Regeneromics, China; ⁴ Wellcome Trust Sanger Institute, UK

Discussion

Schistosomiasis is a neglected tropical disease caused by platyhelminths of the genus Schistosoma. The disease has global impact on human and animal health. According to the WHO, approximately 600 million people live in endemic areas, of which > 200 million require treatment [1]. Schistosomes are the only platyhelminths that have evolved separate sexes, and they exhibit a unique reproductive biology because the female's sexual maturation depends on a constant pairing-contact with the male. Because medical treatment is based upon a single drug, praziquantel, there is urgent need for the development of alternative control strategies.

Due to their proven druggability, G protein-coupled receptors (GPCRs) are promising targets for anthelmintics. However, to identify candidate receptors, a deeper understanding of GPCR signaling in schistosome biology is essential. Comparative transcriptomics of paired and unpaired worms and their gonads revealed 39 differentially regulated GPCR genes putatively involved in neuronal processes [2-3]. In general, the diversity among GPCRs and their integral membrane topology make it difficult to characterize and deorphanize these receptors. To overcome existing limitations we utilized the innovative MALAR yeast two-hybrid assay to associate neuropeptide ligands with their cognate receptors. This method allowed us to identify putative neuropeptides for two GPCRs, which are differentially expressed in a pairing-dependent manner. Besides their value for basic research, insights into the participation of GPCRs/neuropeptides in schistosome biology may also support applied research aspects.

[1] www.who.int/news-room/fact-sheets/detail/schistosomiasis

[2] Lu, Z. et al. (2016). Schistosome sex matters: a deep view into gonad-specific and pairing-dependent transcriptomes reveals a complex gender interplay. Scientific Reports 6, 31150.

[3] Hahnel, S. et al. (2018) Tissue-specific transcriptome analyses provide new insights into GPCR signaling in adult Schistosoma mansoni. PLoS Pathogens 14(1): e1006718