TY - JOUR
T1 - Analysis of Human TAAR8 and Murine Taar8b Mediated Signaling Pathways and Expression Profile
AU - Mühlhaus, Jessica
AU - Dinter, Juliane
AU - Nürnberg, Daniela
AU - Rehders, Maren
AU - Depke, Maren
AU - Golchert, Janine
AU - Homuth, Georg
AU - Yi, Chun-Xia
AU - Morin, Silke
AU - Köhrle, Josef
AU - Brix, Klaudia
AU - Tschöp, Matthias
AU - Kleinau, Gunnar
AU - Biebermann, Heike
PY - 2014
Y1 - 2014
N2 - The thyroid hormone derivative 3-iodothyronamine (3-T(1)AM) exerts metabolic effects in vivo that contradict known effects of thyroid hormones. 3-T(1)AM acts as a trace amine-associated receptor 1 (TAAR1) agonist and activates G(s) signaling in vitro. Interestingly, 3-T(1)AM-meditated in vivo effects persist in Taar1 knockout-mice indicating that further targets of 3-T(1)AM 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 G(s) and/or G(i/o) signaling. Activation of G-proteins G(q/11) and G(12/13) 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-T(1)AM as a ligand for TAAR8 and Taar8b, but both receptors were characterized by a basal G(i/o) signaling activity, a so far unknown signaling pathway for TAARs
AB - The thyroid hormone derivative 3-iodothyronamine (3-T(1)AM) exerts metabolic effects in vivo that contradict known effects of thyroid hormones. 3-T(1)AM acts as a trace amine-associated receptor 1 (TAAR1) agonist and activates G(s) signaling in vitro. Interestingly, 3-T(1)AM-meditated in vivo effects persist in Taar1 knockout-mice indicating that further targets of 3-T(1)AM 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 G(s) and/or G(i/o) signaling. Activation of G-proteins G(q/11) and G(12/13) 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-T(1)AM as a ligand for TAAR8 and Taar8b, but both receptors were characterized by a basal G(i/o) signaling activity, a so far unknown signaling pathway for TAARs
U2 - https://doi.org/10.3390/ijms151120638
DO - https://doi.org/10.3390/ijms151120638
M3 - Article
C2 - 25391046
SN - 1422-0067
VL - 15
SP - 20638
EP - 20655
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 11
ER -