Unique pharmacological properties of serotonergic G-protein coupled receptors from cestodes
Publication Date
February 09, 2018
Authors
Federico Camicia, Ana M. Celentano, Malcolm E. Johns, John D. Chan, et al
Volume
12
Issue
2
Pages
e0006267
DOI
https://dx.plos.org/10.1371/journal.pntd.0006267
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0006267
Scopus
85044350844
Mendeley
http://www.mendeley.com/research/unique-pharmacological-properties-serotoninergic-gprotein-coupled-receptors-cestodes
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Mendeley | Further Information

{"title"=>"Unique pharmacological properties of serotoninergic G-protein coupled receptors from cestodes", "type"=>"journal", "authors"=>[{"first_name"=>"Federico", "last_name"=>"Camicia", "scopus_author_id"=>"12142061400"}, {"first_name"=>"Ana M.", "last_name"=>"Celentano", "scopus_author_id"=>"57201342387"}, {"first_name"=>"Malcolm E.", "last_name"=>"Johns", "scopus_author_id"=>"57189601176"}, {"first_name"=>"John D.", "last_name"=>"Chan", "scopus_author_id"=>"57201439459"}, {"first_name"=>"Lucas", "last_name"=>"Maldonado", "scopus_author_id"=>"56526515300"}, {"first_name"=>"Hugo", "last_name"=>"Vaca", "scopus_author_id"=>"57201337630"}, {"first_name"=>"Nicolás", "last_name"=>"Di Siervi", "scopus_author_id"=>"57193272548"}, {"first_name"=>"Laura", "last_name"=>"Kamentezky", "scopus_author_id"=>"57201334690"}, {"first_name"=>"Ana M.", "last_name"=>"Gamo", "scopus_author_id"=>"36645847500"}, {"first_name"=>"Silvia", "last_name"=>"Ortega-Gutierrez", "scopus_author_id"=>"6602279261"}, {"first_name"=>"Mar", "last_name"=>"Martin-Fontecha", "scopus_author_id"=>"6508099130"}, {"first_name"=>"Carlos", "last_name"=>"Davio", "scopus_author_id"=>"7003730261"}, {"first_name"=>"Jonathan S.", "last_name"=>"Marchant", "scopus_author_id"=>"7103241145"}, {"first_name"=>"Mara C.", "last_name"=>"Rosenzvit", "scopus_author_id"=>"6602900951"}], "year"=>2018, "source"=>"PLoS Neglected Tropical Diseases", "identifiers"=>{"issn"=>"19352735", "scopus"=>"2-s2.0-85044350844", "sgr"=>"85044350844", "pui"=>"621340098", "isbn"=>"1111111111", "pmid"=>"29425245", "doi"=>"10.1371/journal.pntd.0006267"}, "id"=>"7305867e-23c9-3003-a85e-261032720553", "abstract"=>"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.", "link"=>"http://www.mendeley.com/research/unique-pharmacological-properties-serotoninergic-gprotein-coupled-receptors-cestodes", "reader_count"=>4, "reader_count_by_academic_status"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Master"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>1, "Student > Doctoral Student"=>1, "Researcher"=>1, "Student > Master"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Agricultural and Biological Sciences"=>1, "Immunology and Microbiology"=>1}, "reader_count_by_subdiscipline"=>{"Immunology and Microbiology"=>{"Immunology and Microbiology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>1}, "Unspecified"=>{"Unspecified"=>2}}, "group_count"=>0}

Scopus | Further Information

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