RT Journal Article
T1 Unique pharmacological properties of serotoninergic G-protein coupled receptors from cestodes
A1 Camicia, Federico
A1 Celentano, Ana M.
A1 Johns, Malcolm E.
A1 Chan, John D.
A1 Maldonado, Lucas
A1 Vaca, Hugo
A1 Siervi, Nicolás Di
A1 Kamenetzky, Laura
A1 Gamo Albero, Ana María
A1 Ortega Gutiérrez, Silvia
A1 Martín Fontecha, María del Mar
A1 Davio, Carlos
A1 Marchant, Jonathan S.
A1 Rosenzvit, Mara C.
AB Background: Cestodes 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 findings: Three 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/Significance: These data provide the first functional report of GPCRs in parasitic cestodes. The serotoninergic GPCRs characterized here may represent novel druggable targets for antiparasitic intervention.
PB Public Library Science
SN 1932-6203
YR 2018
FD 2018-02-09
LK https://hdl.handle.net/20.500.14352/12026
UL https://hdl.handle.net/20.500.14352/12026
LA eng
NO En O.A. en la web del editor
NO Ministerio de Economía y Competitividad (MINECO)
NO Consejo Nacional de Investigaciones Científicas y Técnicas (COCINET)
NO Ministerio de Innovación, Ciencia y Tecnología de España (MINCyT)
NO Secretaría de Ciencia y Técnica (UBACyT) de Argentina
NO Universidad de Buenos Aires (Argentina)
NO Universidad Complutense de Madrid
DS Docta Complutense
RD 28 abr 2024