Analysis of human TAAR8 and murine Taar8b mediated signaling pathways and expression profile.
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 G(s) 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 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-T1AM 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.
Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. jessica.muehlhaus@charite.de.
Jessica
J
Mühlhaus
Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. juliane.dinter@charite.de.
Juliane
J
Dinter
Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. daniela.nuernberg@charite.de.
Daniela
D
Nürnberg
School of Engineering and Science, Research Center MOLIFE-Molecular Life Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany. m.rehders@jacobs-university.de.
Maren
M
Rehders
Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Fr iedrich-Ludwig-Jahn-Str. 15a, 17487 Greifswald, Germany. depke@uni-greifswald.de.
Maren
M
Depke
Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Fr iedrich-Ludwig-Jahn-Str. 15a, 17487 Greifswald, Germany. janinegolchert@web.de.
Janine
J
Golchert
Interfaculty Institute for Genetics and Functional Genomics, University Medicine and Ernst-Moritz-Arndt-University Greifswald, Fr iedrich-Ludwig-Jahn-Str. 15a, 17487 Greifswald, Germany. georg.homuth@uni-greifswald.de.
Georg
G
Homuth
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Obesity, Business Campus Garching, Parkring 13, 85748 Garching, Germany. chun-xia.yi@helmholtz-muenchen.de.
Chun-Xia
CX
Yi
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Obesity, Business Campus Garching, Parkring 13, 85748 Garching, Germany. silke.morin@helmholtz-muenchen.de.
Silke
S
Morin
Institut für Experimentelle Endokrinologie, Charité-Universitätsmedizin Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. josef.koehrle@charite.de.
Josef
J
Köhrle
School of Engineering and Science, Research Center MOLIFE-Molecular Life Science, Jacobs University Bremen, Campus Ring 1, 28759 Bremen, Germany. k.brix@jacobs-university.de.
Klaudia
K
Brix
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute for Diabetes and Obesity, Business Campus Garching, Parkring 13, 85748 Garching, Germany. matthias.tschoep@helmholtz-muenchen.de.
Matthias
M
Tschöp
Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. gunnar.kleinau@charite.de.
Gunnar
G
Kleinau
Institut für Experimentelle Pädiatrische Endokrinologie, Charité-Universitätsmedizin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353 Berlin, Germany. heike.biebermann@charite.de.
Heike
H
Biebermann
D000818:Animals; D005260:Female; D015870:Gene Expression; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D043562:Receptors, G-Protein-Coupled / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000095383:Trace Amine-Associated Receptors
D043562:Receptors, G-Protein-Coupled; C000599311:TAAR8 protein, human; D000095383:Trace Amine-Associated Receptors; C000599312:Taar8b protein, mouse