{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:27:35Z","timestamp":1789730855596,"version":"4.0.1"},"reference-count":45,"publisher":"Cambridge University Press (CUP)","issue":"8","license":[{"start":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T00:00:00Z","timestamp":1576454400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Schistosomiasis is an acute and chronic disease caused by parasitic worms of the genus <jats:italic>Schistosoma<\/jats:italic>. Treatment is solely dependent on praziquantel. In the face of the worldwide dimension, projects have been initiated to develop new chemotherapies. 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 signalling in schistosome biology is essential. Comparative transcriptomics of paired and unpaired worms and their gonads revealed 59 differentially regulated GPCR-coding genes putatively involved in neuronal processes. 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 performed a pilot approach and utilized the innovative Membrane-Anchored Ligand And Receptor yeast two-hybrid system (MALAR-Y2H) to associate potential neuropeptide ligands with their cognate receptors. Here, we demonstrated the ability to express full-length GPCRs of <jats:italic>Schistosoma mansoni<\/jats:italic> in a heterologous yeast-based system. Additionally, we localized GPCRs and chimeras of neuropeptides fused to the WBP1 transmembrane domain of yeast to the plasma membrane of yeast cells. Reporter gene assays indicated ligand-receptor binding, which allowed us to identify certain neuropeptides as potential ligands for two GPCRs, which had been found before to be differentially expressed in schistosomes in a pairing-dependent manner. Thus, the MALAR-Y2H system appears suitable to unravel schistosome GPCR\u2013ligand interactions. Besides its relevance for understanding schistosome biology, identifying and characterizing GPCR\u2013ligand interaction will also contribute to applied research aspects.<\/jats:p>","DOI":"10.1017\/s0031182019001756","type":"journal-article","created":{"date-parts":[[2019,12,16]],"date-time":"2019-12-16T10:57:03Z","timestamp":1576493823000},"page":"865-872","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":8,"title":["Towards deorphanizing G protein-coupled receptors of <i>Schistosoma mansoni<\/i> using the MALAR yeast two-hybrid system"],"prefix":"10.1017","volume":"147","author":[{"given":"Oliver","family":"Weth","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Haeberlein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Haimann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3144-2026","authenticated-orcid":false,"given":"Christoph G.","family":"Grevelding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2019,12,16]]},"reference":[{"key":"S0031182019001756_ref44","doi-asserted-by":"publisher","DOI":"10.1186\/s12934-015-0203-y"},{"key":"S0031182019001756_ref15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1006718"},{"key":"S0031182019001756_ref8","doi-asserted-by":"publisher","DOI":"10.1007\/BF00930846"},{"key":"S0031182019001756_ref11","first-page":"167","article-title":"Neuropeptide GPCRs in C","volume":"3","author":"Frooninckx","year":"2012","journal-title":"elegans. Frontiers in endocrinology"},{"key":"S0031182019001756_ref34","doi-asserted-by":"publisher","DOI":"10.1016\/S0958-1669(98)80038-4"},{"key":"S0031182019001756_ref10","doi-asserted-by":"publisher","DOI":"10.1038\/340245a0"},{"key":"S0031182019001756_ref29","first-page":"76","article-title":"Parasite neuropeptide biology: Seeding rational drug target selection? International journal for parasitology","volume":"2","author":"McVeigh","year":"2012","journal-title":"Drugs and drug resistance"},{"key":"S0031182019001756_ref22","doi-asserted-by":"publisher","DOI":"10.1038\/srep35631"},{"key":"S0031182019001756_ref2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(90)90085-Z"},{"key":"S0031182019001756_ref9","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ne.15.030192.000421"},{"key":"S0031182019001756_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2009.03.005"},{"key":"S0031182019001756_ref16","doi-asserted-by":"publisher","DOI":"10.1007\/BF01868635"},{"key":"S0031182019001756_ref45","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-12-596"},{"key":"S0031182019001756_ref32","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2004.04494.x"},{"key":"S0031182019001756_ref5","doi-asserted-by":"publisher","DOI":"10.1186\/s40249-017-0286-2"},{"key":"S0031182019001756_ref19","doi-asserted-by":"publisher","DOI":"10.1038\/4310"},{"key":"S0031182019001756_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2008.05.009"},{"key":"S0031182019001756_ref28","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0429com"},{"key":"S0031182019001756_ref23","first-page":"3","article-title":"Presidential address","volume":"88","author":"LoVerde","year":"2002","journal-title":"Sex and schistosomes: an interesting biological interplay with control implications. Journal of Parasitology"},{"key":"S0031182019001756_ref37","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.9.5187"},{"key":"S0031182019001756_ref21","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4922(01)01893-1"},{"key":"S0031182019001756_ref33","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2015.03.005"},{"key":"S0031182019001756_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2008.06.005"},{"key":"S0031182019001756_ref41","doi-asserted-by":"publisher","DOI":"10.1002\/yea.2951"},{"key":"S0031182019001756_ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2015.09.001"},{"key":"S0031182019001756_ref7","doi-asserted-by":"publisher","DOI":"10.1186\/1756-3305-7-242"},{"key":"S0031182019001756_ref13","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/30.8.1851"},{"key":"S0031182019001756_ref17","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.103.1.171"},{"key":"S0031182019001756_ref3","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2010.05.009"},{"key":"S0031182019001756_ref6","doi-asserted-by":"publisher","DOI":"10.1038\/nature08160"},{"key":"S0031182019001756_ref20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2016.05.007"},{"key":"S0031182019001756_ref36","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygcen.2004.12.018"},{"key":"S0031182019001756_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.06.003"},{"key":"S0031182019001756_ref26","doi-asserted-by":"publisher","DOI":"10.1007\/s12033-008-9031-1"},{"key":"S0031182019001756_ref40","first-page":"8","article-title":"An essential 45 kDa yeast transmembrane protein reacts with anti-nuclear pore antibodies: purification of the protein, immunolocalization and cloning of the gene","volume":"56","author":"te Heesen","year":"1991","journal-title":"European journal of cell biology"},{"key":"S0031182019001756_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2011.03.010"},{"key":"S0031182019001756_ref12","doi-asserted-by":"publisher","DOI":"10.1038\/nature01097"},{"key":"S0031182019001756_ref35","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1002457"},{"key":"S0031182019001756_ref14","doi-asserted-by":"publisher","DOI":"10.1016\/0166-6851(94)00058-U"},{"key":"S0031182019001756_ref18","doi-asserted-by":"publisher","DOI":"10.1016\/S0196-9781(01)00602-7"},{"key":"S0031182019001756_ref25","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2019.00796"},{"key":"S0031182019001756_ref24","doi-asserted-by":"publisher","DOI":"10.1038\/srep31150"},{"key":"S0031182019001756_ref43","unstructured":"WHO Global 2016 Disease burden and mortality estimates. Retrieved from: (accessed 4 September 2019)."},{"key":"S0031182019001756_ref42","doi-asserted-by":"publisher","DOI":"10.1099\/mgen.0.000150"},{"key":"S0031182019001756_ref1","doi-asserted-by":"publisher","DOI":"10.1038\/s41587-019-0036-z"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0031182019001756","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,14]],"date-time":"2021-05-14T11:25:29Z","timestamp":1620991529000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0031182019001756\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,16]]},"references-count":45,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,7]]}},"alternative-id":["S0031182019001756"],"URL":"https:\/\/doi.org\/10.1017\/s0031182019001756","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,12,16]]},"assertion":[{"value":"Copyright \u00a9 The Author(s), 2019. Published by Cambridge University Press","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}