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Int. J. Mol. Sci. 2014, 15(11), 20638-20655; doi:10.3390/ijms151120638

Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile

1
Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
2
School of Engineering and Science, Research Center MOLIFE—Molecular Life Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany
3
Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Fr iedrich-Ludwig-Jahn-Str. 15a, 17487 Greifswald, Germany
4
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Obesity, Business Campus Garching, Parkring 13, 85748 Garching, Germany
5
Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany
6
Division of Metabolic Diseases, School of Medicine, Technische Universität München, Schneckenburgerstraße 8, 81675 München, Germany
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 3 August 2014 / Revised: 25 October 2014 / Accepted: 4 November 2014 / Published: 10 November 2014
(This article belongs to the Collection G Protein-Coupled Receptor Signaling and Regulation)
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Abstract

The thyroid hormone derivative 3-iodothyronamine (3-T1AM) exerts metabolic effects in vivo that contradict known effects of thyroid hormones. 3-T1AM acts as a trace amine-associated receptor 1 (TAAR1) agonist and activates Gs signaling in vitro. Interestingly, 3-T1AM-meditated in vivo effects persist in Taar1 knockout-mice indicating that further targets of 3-T1AM might exist. Here, we investigated another member of the TAAR family, the only scarcely studied mouse and human trace-amine-associated receptor 8 (Taar8b, TAAR8). By RT-qPCR and locked-nucleic-acid (LNA) in situ hybridization, Taar8b expression in different mouse tissues was analyzed. Functionally, we characterized TAAR8 and Taar8b with regard to cell surface expression and signaling via different G-protein-mediated pathways. Cell surface expression was verified by ELISA, and cAMP accumulation was quantified by AlphaScreen for detection of Gs and/or Gi/o signaling. Activation of G-proteins Gq/11 and G12/13 was analyzed by reporter gene assays. Expression analyses revealed at most marginal Taar8b expression and no gender differences for almost all analyzed tissues. In heart, LNA-in situ hybridization demonstrated the absence of Taar8b expression. We could not identify 3-T1AM as a ligand for TAAR8 and Taar8b, but both receptors were characterized by a basal Gi/o signaling activity, a so far unknown signaling pathway for TAARs. View Full-Text
Keywords: trace amine-associated receptor; TAAR8; 3-T1AM; thyronamine; signaling pathways; basal activity trace amine-associated receptor; TAAR8; 3-T1AM; thyronamine; signaling pathways; basal activity
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Mühlhaus, J.; Dinter, J.; Nürnberg, D.; Rehders, M.; Depke, M.; Golchert, J.; Homuth, G.; Yi, C.-X.; Morin, S.; Köhrle, J.; Brix, K.; Tschöp, M.; Kleinau, G.; Biebermann, H. Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile. Int. J. Mol. Sci. 2014, 15, 20638-20655.

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Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
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