Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Basic Thyroidology / Original Paper

Free Access

Evolutionary Conservation of 3-Iodothyronamine as an Agonist at the Trace Amine-Associated Receptor 1

Cöster M.a · Biebermann H.b · Schöneberg T.a · Stäubert C.a

Author affiliations

aInstitute of Biochemistry, Faculty of Medicine, University of Leipzig, Leipzig, and bInstitut für Experimenelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin Berlin, Berlin, Germany

Corresponding Author

Claudia Stäubert

Institute of Biochemistry, Molecular Biochemistry

Faculty of Medicine, University of Leipzig

Johannisallee 30, DE-04103 Leipzig (Germany)

E-Mail claudia.staeubert@medizin.uni-leipzig.de

Related Articles for ""

Eur Thyroid J 2015;4(suppl 1):9-20

Do you have an account?

Login Information





Contact Information












By signing up for MyKarger you will automatically participate in our year-End raffle.
If you Then Do Not wish To participate, please uncheck the following box.

Yes, I wish To participate In the year-End raffle And Get the chance To win some Of our most interesting books, And other attractive prizes.


I have read the Karger Terms and Conditions and agree.



Abstract

Objectives: The trace amine-associated receptor 1 (Taar1) is a Gs protein-coupled receptor activated by trace amines, such as β-phenylethylamine (β-PEA) and 3-iodothyronamine (T1AM). T1AM is an endogenous biogenic amine and thyroid hormone derivative that exerts several biological functions. However, the physiological relevance of T1AM acting via Taar1 is still under discussion. Therefore, we studied the structural and functional evolution of Taar1 in vertebrates to provide evidence for a conserved Taar1-mediated T1AM function. Study Design: We searched public sequence databases to retrieve Taar1 sequence information from vertebrates. We cloned and functionally characterized Taar1 from selected vertebrate species using cAMP assays to determine the evolutionary conservation of T1AM action at Taar1. Results: We found intact open reading frames of Taar1 in more than 100 vertebrate species, including mammals, sauropsids and amphibians. Evolutionary conservation analyses of Taar1 protein sequences revealed a high variation in amino acid residues proposed to be involved in agonist binding, especially in rodent Taar1 orthologs. Functional characterization showed that T1AM, β-PEA and p-tyramine (p-Tyr) act as agonists at all tested orthologs, but EC50 values of T1AM at rat Taar1 differed significantly when compared to all other tested vertebrate Taar1. Conclusions: The high structural conservation of Taar1 throughout vertebrate evolution highlights the physiological relevance of Taar1, but species-specific differences in T1AM potency at Taar1 orthologs suggest a specialization of rat Taar1 for T1AM recognition. In contrast, β-PEA and p-Tyr potencies were rather conserved throughout all tested Taar1 orthologs. We provide evidence that the observed differences in potency are related to differences in constraint during Taar1 evolution.

© 2015 European Thyroid Association Published by S. Karger AG, Basel


References

  1. Scanlan TS, Suchland KL, Hart ME, Chiellini G, Huang Y, Kruzich PJ, Frascarelli S, Crossley DA, Bunzow JR, Ronca-Testoni S, Lin ET, Hatton D, Zucchi R, Grandy DK: 3-Iodothyronamine is an endogenous and rapid-acting derivative of thyroid hormone. Nat Med 2004;10:638-642.
  2. Braulke LJ, Klingenspor M, DeBarber A, Tobias SC, Grandy DK, Scanlan TS, Heldmaier G: 3-Iodothyronamine: a novel hormone controlling the balance between glucose and lipid utilisation. J Comp Physiol B 2008;178:167-177.
  3. Chiellini G, Frascarelli S, Ghelardoni S, Carnicelli V, Tobias SC, DeBarber A, Brogioni S, Ronca-Testoni S, Cerbai E, Grandy DK, Scanlan TS, Zucchi R: Cardiac effects of 3-iodothyronamine: a new aminergic system modulating cardiac function. FASEB J 2007;21:1597-1608.
  4. Saba A, Chiellini G, Frascarelli S, Marchini M, Ghelardoni S, Raffaelli A, Tonacchera M, Vitti P, Scanlan TS, Zucchi R: Tissue distribution and cardiac metabolism of 3-iodothyronamine. Endocrinology 2010;151:5063-5073.
  5. Zucchi R, Accorroni A, Chiellini G: Update on 3-iodothyronamine and its neurological and metabolic actions. Front Physiol 2014;5:402.
  6. Borowsky B, Adham N, Jones KA, Raddatz R, Artymyshyn R, Ogozalek KL, Durkin MM, Lakhlani PP, Bonini JA, Pathirana S, Boyle N, Pu X, Kouranova E, Lichtblau H, Ochoa FY, Branchek TA, Gerald C: Trace amines: identification of a family of mammalian G protein-coupled receptors. Proc Natl Acad Sci USA 2001;98:8966-8971.
  7. Bunzow JR, Sonders MS, Arttamangkul S, Harrison LM, Zhang G, Quigley DI, Darland T, Suchland KL, Pasumamula S, Kennedy JL, Olson SB, Magenis RE, Amara SG, Grandy DK: Amphetamine, 3,4-methylenedioxymethamphetamine, lysergic acid diethylamide, and metabolites of the catecholamine neurotransmitters are agonists of a rat trace amine receptor. Mol Pharmacol 2001;60:1181-1188.
  8. D'Andrea G, Terrazzino S, Fortin D, Farruggio A, Rinaldi L, Leon A: HPLC electrochemical detection of trace amines in human plasma and platelets and expression of mRNA transcripts of trace amine receptors in circulating leukocytes. Neurosci Lett 2003;346:89-92.
  9. Zucchi R, Chiellini G, Scanlan TS, Grandy DK: Trace amine-associated receptors and their ligands. Br J Pharmacol 2006;149:967-978.
  10. Lindemann L, Hoener MC: A renaissance in trace amines inspired by a novel GPCR family. Trends Pharmacol Sci 2005;26:274-281.
  11. Wainscott DB, Little SP, Yin T, Tu Y, Rocco VP, He JX, Nelson DL: Pharmacologic characterization of the cloned human trace amine-associated receptor1 (TAAR1) and evidence for species differences with the rat TAAR1. J Pharmacol Exp Ther 2007;320:475-485.
  12. Reese EA, Bunzow JR, Arttamangkul S, Sonders MS, Grandy DK: Trace amine-associated receptor 1 displays species-dependent stereoselectivity for isomers of methamphetamine, amphetamine, and para-hydroxyamphetamine. J Pharmacol Exp Ther 2007;321:178-186.
  13. Gloriam DE, Bjarnadottir TK, Yan YL, Postlethwait JH, Schioth HB, Fredriksson R: The repertoire of trace amine G-protein-coupled receptors: large expansion in zebrafish. Mol Phylogenet Evol 2005;35:470-482.
  14. Okayama H, Berg P: A cDNA cloning vector that permits expression of cDNA inserts in mammalian cells. Mol Cell Biol 1983;3:280-289.
  15. Thompson JD, Higgins DG, Gibson TJ: CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 1994;22:4673-4680.
  16. Kimura M: A simple method for estimating evolutionary rates of base substitutions through comparative studies of nucleotide sequences. J Mol Evol 1980;16:111-120.
  17. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S: MEGA6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 2013;30:2725-2729.
  18. Yang Z: PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 2007;24:1586-1591.
  19. Yang Z: Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 1998;15:568-573.
  20. Li C, Wen A, Shen B, Lu J, Huang Y, Chang Y: FastCloning: a highly simplified, purification-free, sequence- and ligation-independent PCR cloning method. BMC Biotechnol 2011;11:92.
  21. Schöneberg T, Schulz A, Biebermann H, Gruters A, Grimm T, Hubschmann K, Filler G, Gudermann T, Schultz G: V2 vasopressin receptor dysfunction in nephrogenic diabetes insipidus caused by different molecular mechanisms. Hum Mutat 1998;12:196-205.
  22. Tan ES, Miyakawa M, Bunzow JR, Grandy DK, Scanlan TS: Exploring the structure-activity relationship of the ethylamine portion of 3-iodothyronamine for rat and mouse trace amine-associated receptor 1. J Med Chem 2007;50:2787-2798.
  23. Tan ES, Naylor JC, Groban ES, Bunzow JR, Jacobson MP, Grandy DK, Scanlan TS: The molecular basis of species-specific ligand activation of trace amine-associated receptor 1 (TAAR1). ACS Chem Biol 2009;4:209-220.
  24. Tessarolo JA, Tabesh MJ, Nesbitt M, Davidson WS: Genomic organization and evolution of the trace amine-associated receptor (TAAR) repertoire in Atlantic salmon (Salmo salar). G3 2014;4:1135-1141.
  25. Vallender EJ, Xie Z, Westmoreland SV, Miller GM: Functional evolution of the trace amine associated receptors in mammals and the loss of TAAR1 in dogs. BMC Evol Biol 2010;10:51.
  26. Tamura K, Peterson D, Peterson N, Stecher G, Nei M, Kumar S: MEGA5: molecular evolutionary genetics analysis using maximum likelihood, evolutionary distance, and maximum parsimony methods. Mol Biol Evol 2011;28:2731-2739.
  27. Yang Z, Nielsen R: Codon-substitution models for detecting molecular adaptation at individual sites along specific lineages. Mol Biol Evol 2002;19:908-917.
  28. Zhang J, Nielsen R, Yang Z: Evaluation of an improved branch-site likelihood method for detecting positive selection at the molecular level. Mol Biol Evol 2005;22:2472-2479.
  29. Rovati GE, Capra V, Neubig RR: The highly conserved DRY motif of class a G protein-coupled receptors: beyond the ground state. Mol Pharmacol 2007;71:959-964.
  30. Gaillard I, Rouquier S, Chavanieu A, Mollard P, Giorgi D: Amino-acid changes acquired during evolution by olfactory receptor 912-93 modify the specificity of odorant recognition. Hum Mol Genet 2004;13:771-780.
  31. Reese EA, Norimatsu Y, Grandy MS, Suchland KL, Bunzow JR, Grandy DK: Exploring the determinants of trace amine-associated receptor 1's functional selectivity for the stereoisomers of amphetamine and methamphetamine. J Med Chem 2014;57:378-390.
  32. Cichero E, Espinoza S, Gainetdinov RR, Brasili L, Fossa P: Insights into the structure and pharmacology of the human trace amine-associated receptor 1 (hTAAR1): homology modelling and docking studies. Chem Biol Drug Des 2013;81:509-516.
  33. Roy G, Placzek E, Scanlan TS: ApoB-100-containing lipoproteins are major carriers of 3-iodothyronamine in circulation. J Biol Chem 2012;287:1790-1800.
  34. Cumero S, Fogolari F, Domenis R, Zucchi R, Mavelli I, Contessi S: Mitochondrial F0F1-atp synthase is a molecular target of 3-iodothyronamine, an endogenous metabolite of thyroid hormone. Br J Pharmacol 2012;166:2331-2347.
  35. Ianculescu AG, Friesema EC, Visser TJ, Giacomini KM, Scanlan TS: Transport of thyroid hormones is selectively inhibited by 3-iodothyronamine. Mol Biosyst 2010;6:1403-1410.
  36. Ianculescu AG, Giacomini KM, Scanlan TS: Identification and characterization of 3-iodothyronamine intracellular transport. Endocrinology 2009;150:1991-1999.
  37. Panas HN, Lynch LJ, Vallender EJ, Xie Z, Chen GL, Lynn SK, Scanlan TS, Miller GM: Normal thermoregulatory responses to 3-iodothyronamine, trace amines and amphetamine-like psychostimulants in trace amine associated receptor 1 knockout mice. J Neurosci Res 2010;88:1962-1969.
  38. Galli E, Marchini M, Saba A, Berti S, Tonacchera M, Vitti P, Scanlan TS, Iervasi G, Zucchi R: Detection of 3-iodothyronamine in human patients: a preliminary study. J Clin Endocrinol Metab 2012;97:E69-E74.
  39. Kenakin T: Recombinant roulette versus the apparent virtues of ‘natural' cell receptor systems: receptor genotypes versus phenotypes. Trends Pharmacol Sci 2002;23:403-404.
  40. Lindemann L, Ebeling M, Kratochwil NA, Bunzow JR, Grandy DK, Hoener MC: Trace amine-associated receptors form structurally and functionally distinct subfamilies of novel G protein-coupled receptors. Genomics 2005;85:372-385.
  41. Jones DT, Taylor WR, Thornton JM: The rapid generation of mutation data matrices from protein sequences. Comput Appl Biosci 1992;8:275-282.

Article / Publication Details

First-Page Preview
Abstract of Basic Thyroidology / Original Paper

Received: November 17, 2014
Accepted: April 21, 2015
Published online: May 29, 2015
Issue release date: September 2015

Number of Print Pages: 12
Number of Figures: 3
Number of Tables: 2

ISSN: 2235-0640 (Print)
eISSN: 2235-0802 (Online)

For additional information: https://www.karger.com/ETJ


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.