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

Autor: Jessica Mühlhaus, Juliane Dinter, Daniela Nürnberg, Maren Rehders, Maren Depke, Janine Golchert, Georg Homuth, Chun-Xia Yi, Silke Morin, Josef Köhrle, Klaudia Brix, Matthias Tschöp, Gunnar Kleinau, Heike Biebermann
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Zdroj: International Journal of Molecular Sciences, Vol 15, Iss 11, Pp 20638-20655 (2014)
Druh dokumentu: article
ISSN: 1422-0067
15112063
DOI: 10.3390/ijms151120638
Popis: 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.
Databáze: Directory of Open Access Journals
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