RRC ID 81113
著者 Rinne MK, Urvas L, Mandrika I, Fridmanis D, Riddy DM, Langmead CJ, Kukkonen JP, Xhaard H.
タイトル Characterization of a putative orexin receptor in Ciona intestinalis sheds light on the evolution of the orexin/hypocretin system in chordates.
ジャーナル Sci Rep
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.
巻・号 14(1)
ページ 7690
公開日 2024-4-2
DOI 10.1038/s41598-024-56508-1
PII 10.1038/s41598-024-56508-1
PMID 38565870
PMC PMC10987541
MeSH Animals Carrier Proteins / metabolism Ciona intestinalis* / genetics Ciona intestinalis* / metabolism HEK293 Cells Humans Orexin Receptors / genetics Orexin Receptors / metabolism Orexins / genetics Orexins / metabolism Signal Transduction Vertebrates / metabolism
IF 3.998
リソース情報
遺伝子材料 NBRP Ciona EST clone citb011b12