Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile
AbstractThe 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
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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.
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. International Journal of Molecular Sciences. 2014; 15(11):20638-20655.Chicago/Turabian Style
Mühlhaus, Jessica; Dinter, Juliane; Nürnberg, Daniela; Rehders, Maren; Depke, Maren; Golchert, Janine; Homuth, Georg; Yi, Chun-Xia; Morin, Silke; Köhrle, Josef; Brix, Klaudia; Tschöp, Matthias; Kleinau, Gunnar; Biebermann, Heike. 2014. "Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile." Int. J. Mol. Sci. 15, no. 11: 20638-20655.