Abstract
BackgroundCestodes are a diverse group of parasites, some of them being agents of neglected diseases. In cestodes, little is known about the functional properties of G protein coupled receptors (GPCRs) which have proved to be highly druggable targets in other organisms. Notably, serotoninergic G-protein coupled receptors (5-HT GPCRs) play major roles in key functions like movement, development and reproduction in parasites.Methodology/Principal findingsThree 5-HT GPCRs from Echinococcus granulosus and Mesocestoides corti were cloned, sequenced, bioinformatically analyzed and functionally characterized. Multiple sequence alignment with other GPCRs showed the presence of seven transmembrane segments and conserved motifs but interesting differences were also observed. Phylogenetic analysis grouped these new sequences within the 5-HT7 clade of GPCRs. Molecular modeling showed a striking resemblance in the spatial localization of key residues with their mammalian counterparts. Expression analysis using available RNAseq data showed that both E. granulosus sequences are expressed in larval and adult stages. Localization studies performed in E. granulosus larvae with a fluorescent probe produced a punctiform pattern concentrated in suckers. E. granulosus and M. corti larvae showed an increase in motility in response to serotonin. Heterologous expression revealed elevated levels of cAMP production in response to 5-HT and two of the GPCRs showed extremely high sensitivity to 5-HT (picomolar range). While each of these GPCRs was activated by 5-HT, they exhibit distinct pharmacological properties (5-HT sensitivity, differential responsiveness to ligands).Conclusions/SignificanceThese data provide the first functional report of GPCRs in parasitic cestodes. The serotoninergic GPCRs characterized here may represent novel druggable targets for antiparasitic intervention.
Highlights
IntroductionThe parasitic flatworms Echinococcus granulosus sensu lato (s. l.) and Mesocestoides corti are tapeworms belonging to the class Cestoda, with E. granulosus s. l. belonging to Taeniidae and M. corti to Mesocestoididae family
These new receptors exhibit unique characteristics including a particular sensitivity to serotonin as well as a distinctive pharmacology, which will assist their targeting for chemotherapeutic intervention
The parasitic flatworms Echinococcus granulosus sensu lato (s. l.) and Mesocestoides corti are tapeworms belonging to the class Cestoda, with E. granulosus s. l. belonging to Taeniidae and M. corti to Mesocestoididae family
Summary
The parasitic flatworms Echinococcus granulosus sensu lato (s. l.) and Mesocestoides corti are tapeworms belonging to the class Cestoda, with E. granulosus s. l. belonging to Taeniidae and M. corti to Mesocestoididae family. The larval stage (tetrathyridia) of M. corti has a remarkable capacity of asexual reproduction in the peritoneal cavity of mice and some other mammalian hosts [2]. This parasite is a well established model for laboratory studies and the tetrathyridium is used to examine drug effects on neuromuscular activity [3]. Any interference with coordination of the parasite movement could result in conveyance to an environment hostile for their survival or expulsion from the host [6] These important functions can be accomplished only by the activity of different kind of muscles [7] innervated by a well-developed nervous system. Serotoninergic G-protein coupled receptors (5-HT GPCRs) play major roles in key functions like movement, development and reproduction in parasites
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
