title: Origin of secretin receptor precedes the advent of tetrapoda: evidence on the separated origins of secretin and orexin.
abstract: At present, secretin and its receptor have only been identified in mammals, and the origin of this ligand-receptor pair in early vertebrates is unclear. In addition, the elusive similarities of secretin and orexin in terms of both structures and functions suggest a common ancestral origin early in the vertebrate lineage. In this article, with the cloning and functional characterization of secretin receptors from lungfish and X. laevis as well as frog (X. laevis and Rana rugulosa) secretins, we provide evidence that the secretin ligand-receptor pair has already diverged and become highly specific by the emergence of tetrapods. The secretin receptor-like sequence cloned from lungfish indicates that the secretin receptor was descended from a VPAC-like receptor prior the advent of sarcopterygians. To clarify the controversial relationship of secretin and orexin, orexin type-2 receptor was cloned from X. laevis. We demonstrated that, in frog, secretin and orexin could activate their mutual receptors, indicating their coordinated complementary role in mediating physiological processes in non-mammalian vertebrates. However, among the peptides in the secretin/glucagon superfamily, secretin was found to be the only peptide that could activate the orexin receptor. We therefore hypothesize that secretin and orexin are of different ancestral origins early in the vertebrate lineage.
authors.affiliation: School of Biological Sciences, Research Centre of Heart, Brain, Hormone and Healthy Ageing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
authors.forename: Janice K V
authors.initials: JK
authors.lastname: Tam
authors.forename: Kwan-Wa
authors.initials: KW
authors.lastname: Lau
authors.forename: Leo T O
authors.initials: LT
authors.lastname: Lee
authors.forename: Jessica Y S
authors.initials: JY
authors.lastname: Chu
authors.forename: Kwong-Man
authors.initials: KM
authors.lastname: Ng
authors.forename: Alain
authors.initials: A
authors.lastname: Fournier
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Billy K C
authors.initials: BK
authors.lastname: Chow
mesh_terms: D000818:Animals; D005075:Biological Evolution; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008024:Ligands; D008297:Male; D008954:Models, Biological; D009479:Neuropeptides / Q000235:genetics*; D000068797:Orexins; D011898:Ranidae; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*; D012633:Secretin / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution; D014982:Xenopus laevis
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D009479:Neuropeptides; D000068797:Orexins; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; C029937:secretin receptor; D012633:Secretin