Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates
Abstract Tunicates are evolutionary model organisms bridging the gap between vertebrates and invertebrates. A genomic sequence in Ciona intestinalis (CiOX) shows high similarity to vertebrate orexin receptors and protostome allatotropin receptors (ATR). Here, molecular phylogeny suggested that CiOX...
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Nature Portfolio
2024-04-01
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| Online Access: | https://doi.org/10.1038/s41598-024-56508-1 |
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| author | Maiju K. Rinne Lauri Urvas Ilona Mandrika Dāvids Fridmanis Darren M. Riddy Christopher J. Langmead Jyrki P. Kukkonen Henri Xhaard |
| author_facet | Maiju K. Rinne Lauri Urvas Ilona Mandrika Dāvids Fridmanis Darren M. Riddy Christopher J. Langmead Jyrki P. Kukkonen Henri Xhaard |
| author_sort | Maiju K. Rinne |
| collection | DOAJ |
| description | Abstract Tunicates are evolutionary model organisms bridging the gap between vertebrates and invertebrates. A genomic sequence in Ciona intestinalis (CiOX) shows high similarity to vertebrate orexin receptors and protostome allatotropin receptors (ATR). Here, molecular phylogeny suggested that CiOX is divergent from ATRs and human orexin receptors (hOX1/2). However, CiOX appears closer to hOX1/2 than to ATR both in terms of sequence percent identity and in its modelled binding cavity, as suggested by molecular modelling. CiOX was heterologously expressed in a recombinant HEK293 cell system. Human orexins weakly but concentration-dependently activated its Gq signalling (Ca2+ elevation), and the responses were inhibited by the non-selective orexin receptor antagonists TCS 1102 and almorexant, but only weakly by the OX1-selective antagonist SB-334867. Furthermore, the 5-/6-carboxytetramethylrhodamine (TAMRA)-labelled human orexin-A was able to bind to CiOX. Database mining was used to predict a potential endogenous C. intestinalis orexin peptide (Ci-orexin-A). Ci-orexin-A was able to displace TAMRA-orexin-A, but not to induce any calcium response at the CiOX. Consequently, we suggested that the orexin signalling system is conserved in Ciona intestinalis, although the relevant peptide-receptor interaction was not fully elucidated. |
| first_indexed | 2024-04-24T12:39:12Z |
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| id | doaj.art-3532f53292dc43e187ca5d3298309620 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-24T12:39:12Z |
| publishDate | 2024-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-3532f53292dc43e187ca5d32983096202024-04-07T11:18:28ZengNature PortfolioScientific Reports2045-23222024-04-0114111510.1038/s41598-024-56508-1Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordatesMaiju K. Rinne0Lauri Urvas1Ilona Mandrika2Dāvids Fridmanis3Darren M. Riddy4Christopher J. Langmead5Jyrki P. Kukkonen6Henri Xhaard7Drug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of HelsinkiDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of HelsinkiLatvian Biomedical Research and Study CentreLatvian Biomedical Research and Study CentreDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash UniversityBiochemistry and Cell Biology, Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of HelsinkiDrug Research Program, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of HelsinkiAbstract Tunicates are evolutionary model organisms bridging the gap between vertebrates and invertebrates. A genomic sequence in Ciona intestinalis (CiOX) shows high similarity to vertebrate orexin receptors and protostome allatotropin receptors (ATR). Here, molecular phylogeny suggested that CiOX is divergent from ATRs and human orexin receptors (hOX1/2). However, CiOX appears closer to hOX1/2 than to ATR both in terms of sequence percent identity and in its modelled binding cavity, as suggested by molecular modelling. CiOX was heterologously expressed in a recombinant HEK293 cell system. Human orexins weakly but concentration-dependently activated its Gq signalling (Ca2+ elevation), and the responses were inhibited by the non-selective orexin receptor antagonists TCS 1102 and almorexant, but only weakly by the OX1-selective antagonist SB-334867. Furthermore, the 5-/6-carboxytetramethylrhodamine (TAMRA)-labelled human orexin-A was able to bind to CiOX. Database mining was used to predict a potential endogenous C. intestinalis orexin peptide (Ci-orexin-A). Ci-orexin-A was able to displace TAMRA-orexin-A, but not to induce any calcium response at the CiOX. Consequently, we suggested that the orexin signalling system is conserved in Ciona intestinalis, although the relevant peptide-receptor interaction was not fully elucidated.https://doi.org/10.1038/s41598-024-56508-1OrexinHypocretinCalciumReceptor bindingCiona intestinalis |
| spellingShingle | Maiju K. Rinne Lauri Urvas Ilona Mandrika Dāvids Fridmanis Darren M. Riddy Christopher J. Langmead Jyrki P. Kukkonen Henri Xhaard Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates Scientific Reports Orexin Hypocretin Calcium Receptor binding Ciona intestinalis |
| title | Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates |
| title_full | Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates |
| title_fullStr | Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates |
| title_full_unstemmed | Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates |
| title_short | Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates |
| title_sort | characterization of a putative orexin receptor in ciona intestinalis sheds light on the evolution of the orexin hypocretin system in chordates |
| topic | Orexin Hypocretin Calcium Receptor binding Ciona intestinalis |
| url | https://doi.org/10.1038/s41598-024-56508-1 |
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