Tissue-specific transcriptome analyses provide new insights into GPCR signalling in adult Schistosoma mansoni

Abstract

Schistosomes are blood-dwelling trematodes with global impact on human and animal health. Because medical treatment is currently based on a single drug, praziquantel, there is urgent need for the development of alternative control strategies. The Schistosoma mansoni genome project provides a platform to study and connect the genetic repertoire of schistosomes to specific biological functions essential for successful parasitism. G protein–coupled receptors (GPCRs) form the largest superfamily of transmembrane receptors throughout the Eumetazoan phyla, including platyhelminths. Due to their involvement in diverse biological processes, their pharmacological importance, and proven druggability, GPCRs are promising targets for new anthelmintics. However, to identify candidate receptors, a more detailed understanding of the roles of GPCR signalling in schistosome biology is essential. An updated phylogenetic analysis of the S. mansoni GPCR genome (GPCRome) is presented, facilitated by updated genome data that allowed a more precise annotation of GPCRs. Additionally, we review the current knowledge on GPCR signalling in this parasite and provide new insights into the potential roles of GPCRs in schistosome reproduction based on the findings of a recent tissue-specific transcriptomic study in paired and unpaired S. mansoni. According to the current analysis, GPCRs contribute to gonad-specific functions but also to nongonad, pairing-dependent processes. The latter may regulate gonad-unrelated functions during the multifaceted male–female interaction. Finally, we compare the schistosome GPCRome to that of another parasitic trematode, Fasciola, and discuss the importance of GPCRs to basic and applied research. Phylogenetic analyses display GPCR diversity in free-living and parasitic platyhelminths and suggest diverse functions in schistosomes. Although their roles need to be substantiated by functional studies in the future, the data support the selection of GPCR candidates for basic and applied studies, invigorating the exploitation of this important receptor class for drug discovery against schistosomes but also other trematodes.

Proteomic and deep sequencing analysis of extracellular vesicles isolated from adult male and female Schistosoma japonicum

“…The large number of eggs produced by mature females plays a central role in the pathology of infection with this parasite and in disease spread. Previous research suggested that the sexual development of the female schistosome depends on appropriate signals provided directly or indirectly by the male during pairing [4][5][6][7][8][9][10][11][12][13]. Thus, understanding the mechanism of female development as a consequence of pairing may lead to novel concepts for impeding egg production to lessen the spread of schistosomiasis.…”

Octopamine signaling in the metazoan pathogen S chistosoma mansoni: localization, small-molecule screening and opportunities for drug development

“…BAs typically signal through G-protein-coupled receptors (GPCRs), however, the current knowledge of BA GPCRs in schistosomes is fragmented ( Hahnel et al, 2018 ). DA, HA and 5HT GPCRs have been characterized in S. mansoni ( Taman and Ribeiro, 2009 ; El-Shehabi and Ribeiro, 2010 ; El-Shehabi et al, 2012 ; Patocka et al, 2014 ).…”

Thein vivotranscriptome ofSchistosoma mansoniin two prominent vector species,Biomphalaria pfeifferiandB. glabrata

“…576 In adult worms, GFVRIamide is localized to neurons that run along the cerebral commissure 577 towards the oral sucker [89]. Allatostatin receptor, a GPCR with ovary-specific transcription in 578 adult S. mansoni [86], is important for reproductive development in Schistosoma japonicum 579 adult females [91]. Four transcripts homologous to allatostatin receptor were expressed 580 primarily in shedding S. mansoni replicates.…”

“…Praziquantel has been identified as a GPCR ligand acting to modulate serotoninergic 538 signaling[83]. Several in silico studies identifying and characterizing the S. mansoni 539 "GPCRome"[84,85] culminated in the classification of a broad range of phylogenetically distinct 540 clades/classes of GPCRs[86]. S. mansoni microarray studies have reported diverse expression 541 patterns of individual GPCRs, with the overall highest expression occurring in 3-7 week worms,542 indicating that they are associated with complex stage-specific roles[29,86].543 In intramolluscan stages, we identified 78 GPCR transcripts from our Illumina samples, and 544 26 probes from microarray samples(Fig 8).…”

“…Several in silico studies identifying and characterizing the S. mansoni 539 "GPCRome"[84,85] culminated in the classification of a broad range of phylogenetically distinct 540 clades/classes of GPCRs[86]. S. mansoni microarray studies have reported diverse expression 541 patterns of individual GPCRs, with the overall highest expression occurring in 3-7 week worms,542 indicating that they are associated with complex stage-specific roles[29,86].543 In intramolluscan stages, we identified 78 GPCR transcripts from our Illumina samples, and 544 26 probes from microarray samples(Fig 8). Many (38%) of the Illumina GPCR transcripts were 545 A FLPR-like, a GPCR class containing receptors similar to FMRFamide GPCRs that invoke 546 muscle fiber contractions in schistosomes by increasing calcium transport across voltage-gated 547 calcium channels[87].…”